Skip to main content
SpringerLink
Log in

Perspectives and Molecular Understanding of Pancreatic Cancer Stem Cells

  • Chapter
  • First Online:
Exploring Pancreatic Metabolism and Malignancy

  • 294 Accesses

Abstract

Pancreatic cancer (PC) is a lethal, malignant cancer that bears high mortality rates. Due to its lack of noticeable symptoms, it is often diagnosed late and current pancreatic cancer therapies are ineffective with poor prognosis. Despite the high mortality and poor survival of PC patients, there is limited information on factors propagating resistance. Resistance to standard therapies in pancreatic cancer patients is partly associated with the presence of a subpopulation of highly plastic “stem-like” cells (pancreatic cancer stem cells: paCSC) in tumors. In this connection, it is important to have a strong understanding of the paCSC population, especially its distinct characteristics, in order to engineer new therapies to target these resistant cells. Therefore, the purpose of this investigation is to highlight and discuss PaCSC and their specific surface markers. Overall, in this study, we searched MEDLINE, EMBASE, the Cochrane Library, Web of Science, and ISI Proceedings for observational studies relating to the PaCSC and PC. Pancreatic cancer stem cells exhibit specific immune characteristics on their surface. The CD133, CD44, CD24, ALDH1, c-Met, DCLK1, CXCR4, EpCAM and ABCG2 are prominent Pa-CSC markers. As PaCSCs drive tumorigenesis and metastasis, their manipulation approaches would have widespread clinical implications and hence improve outcomes in pancreatic cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

15-PGDH:

15-Hydroxyprostaglandin dehydrogenase

5-FU:

5-fluorouracil

ABCG2:

ATP-binding cassette subfamily G member 2

ADLH:

Aldehyde dehydrogenase

ALCAM:

leukocyte cell adhesion molecule

CSCs:

Cancer stem cells

CXCR4:

C-X-C chemokine receptor type 4

DCLK1:

Doublecortin-like kinase 1

EMT:

Epithelial mesenchymal transition

EpCAM:

Epithelial cell adhesion molecule

HA:

hyaluronic acid

HGF:

Hepatocyte growth factor

mRNA:

Messenger RNA

nab-paclitaxel:

albumin-bound paclitaxel

NETs:

Neuroendocrine tumors

NOD/SCID:

nonobese diabetic/severe combined immunodeficiency

PaCSCs:

Pancreatic cancer stem cells

PC:

Pancreatic cancer

PDAC:

pancreatic ductal adenocarcinoma

PDX1:

pancreatic and duodenal homeobox 1

SP:

side-population

TME:

Tumor microenvironment

References

  1. Adamska A, Domenichini A, Falasca M (2017) Pancreatic ductal adenocarcinoma: current and evolving therapies. Int J Mol Sci 18:1338

    Article  PubMed Central  CAS  Google Scholar 

  2. Akita H, Nagano H, Takeda Y, Eguchi H, Wada H, Kobayashi S, Marubashi S, Tanemura M, Takahashi H, Ohigashi H, Tomita Y, Ishikawa O, Mori M, Doki Y (2011) Ep-CAM is a significant prognostic factor in pancreatic cancer patients by suppressing cell activity. Oncogene 30:3468–3476

    Article  CAS  PubMed  Google Scholar 

  3. Aliebrahimi S, Kouhsari SM, Arab SS, Shadboorestan A, Ostad SN (2018) Phytochemicals, withaferin A and carnosol, overcome pancreatic cancer stem cells as c-Met inhibitors. Biomed Pharmacother 106:1527–1536

    Article  CAS  PubMed  Google Scholar 

  4. Amundadottir LT (2016) Pancreatic cancer genetics. Int J Biol Sci 12:314–325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ansari D, Tingstedt B, Andersson B, Holmquist F, Sturesson C, Williamsson C, Sasor A, Borg D, Bauden M, Andersson R (2016) Pancreatic cancer: yesterday, today and tomorrow. Future Oncol 12:1929–1946

    Article  CAS  PubMed  Google Scholar 

  6. Arima K, Ohmuraya M, Miyake K, Koiwa M, Uchihara T, Izumi D, Gao F, Yonemura A, Bu L, Okabe H, Imai K, Hashimoto D, Baba Y, Chikamoto A, Yamashita YI, Furukawa T, Araki K, Baba H, Ishimoto T (2019) Inhibition of 15-PGDH causes Kras-driven tumor expansion through prostaglandin E2-ALDH1 signaling in the pancreas. Oncogene 38:1211–1224

    Article  CAS  PubMed  Google Scholar 

  7. Au A, Aziz Baba A, Goh AS, Wahid Fadilah SA, Teh A, Rosline H, Ankathil R (2014) Association of genotypes and haplotypes of multi-drug transporter genes ABCB1 and ABCG2 with clinical response to imatinib mesylate in chronic myeloid leukemia patients. Biomed Pharmacother 68:343–349

    Article  CAS  PubMed  Google Scholar 

  8. Bailey JM, Alsina J, Rasheed ZA, McAllister FM, Fu YY, Plentz R, Zhang H, Pasricha PJ, Bardeesy N, Matsui W, Maitra A, Leach SD (2014) DCLK1 marks a morphologically distinct subpopulation of cells with stem cell properties in preinvasive pancreatic cancer. Gastroenterology 146:245–256

    Article  CAS  PubMed  Google Scholar 

  9. Balkwill F (2004) The significance of cancer cell expression of the chemokine receptor CXCR4. Semin Cancer Biol 14:171–179

    Article  CAS  PubMed  Google Scholar 

  10. Bhagwandin VJ, Bishop JM, Wright WE, Shay JW (2016) The metastatic potential and chemoresistance of human pancreatic cancer stem cells. PLoS One 11:e0148807

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730–737

    Article  CAS  PubMed  Google Scholar 

  12. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer J Clin 68:394–424

    Google Scholar 

  13. Chatterjee S, Behnam Azad B, Nimmagadda S (2014) The intricate role of CXCR4 in cancer. Adv Cancer Res 124:31–82

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Chen Z, Che Q, He X, Wang F, Wang H, Zhu M, Sun J, Wan X (2015) Stem cell protein Piwil1 endowed endometrial cancer cells with stem-like properties via inducing epithelial-mesenchymal transition. BMC Cancer 15:811

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Chen F, Roberts NJ, Klein AP (2017) Inherited pancreatic cancer. Chin Clin Oncol 6:58–58

    Article  PubMed  PubMed Central  Google Scholar 

  16. Costa MJ, Kudaravalli J, Ma JT, Ho WH, Delaria K, Holz C, Stauffer A, Chunyk AG, Zong Q, Blasi E, Buetow B, Tran TT, Lindquist K, Dorywalska M, Rajpal A, Shelton DL, Strop P, Liu SH (2019) Optimal design, anti-tumour efficacy and tolerability of anti-CXCR4 antibody drug conjugates. Sci Rep 9:2443

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Deng S, Yang X, Lassus H, Liang S, Kaur S, Ye Q, Li C, Wang LP, Roby KF, Orsulic S, Connolly DC, Zhang Y, Montone K, Butzow R, Coukos G, Zhang L (2010) Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform 1 (ALDH1), in human epithelial cancers. PLoS One 5:e10277

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Dimova I, Karthik S, Makanya A, Hlushchuk R, Semela D, Volarevic V, Djonov V (2019) SDF-1/CXCR4 signalling is involved in blood vessel growth and remodelling by intussusception. J Cell Mol Med 23:3916–3926

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ding Q, Yoshimitsu M, Kuwahata T, Maeda K, Hayashi T, Obara T, Miyazaki Y, Matsubara S, Natsugoe S, Takao S (2012) Establishment of a highly migratory subclone reveals that CD133 contributes to migration and invasion through epithelial-mesenchymal transition in pancreatic cancer. Hum Cell 25:1–8

    Article  PubMed  CAS  Google Scholar 

  20. Fan M, Qian N, Dai G (2017) Expression and prognostic significance of doublecortin-like kinase 1 in patients with hepatocellular carcinoma. Oncol Lett 14:7529–7537

    PubMed  PubMed Central  Google Scholar 

  21. Fargeas CA, Florek M, Huttner WB, Corbeil D (2003) Characterization of prominin-2, a new member of the prominin family of pentaspan membrane glycoproteins. J Biol Chem 278:8586–8596

    Article  CAS  PubMed  Google Scholar 

  22. Fazi B, Proserpio C, Galardi S, Annesi F, Cola M, Mangiola A, Michienzi A, Ciafre SA (2019) The expression of the chemokine CXCL14 correlates with several aggressive aspects of glioblastoma and promotes key properties of glioblastoma cells. Int J Mol Sci 20. https://doi.org/10.3390/ijms20102496

    Article  PubMed Central  CAS  Google Scholar 

  23. Florek M, Bauer N, Janich P, Wilsch-Braeuninger M, Fargeas CA, Marzesco AM, Ehninger G, Thiele C, Huttner WB, Corbeil D (2007) Prominin-2 is a cholesterol-binding protein associated with apical and basolateral plasmalemmal protrusions in polarized epithelial cells and released into urine. Cell Tissue Res 328:31–47

    Article  CAS  PubMed  Google Scholar 

  24. Fu Z, Chen C, Zhou Q, Wang Y, Zhao Y, Zhao X, Li W, Zheng S, Ye H, Wang L, He Z, Lin Q, Li Z, Chen R (2017) LncRNA HOTTIP modulates cancer stem cell properties in human pancreatic cancer by regulating HOXA9. Cancer Lett 410:68–81

    Article  CAS  PubMed  Google Scholar 

  25. Fujiwara K, Ohuchida K, Sada M, Horioka K, Ulrich CD 3rd, Shindo K, Ohtsuka T, Takahata S, Mizumoto K, Oda Y, Tanaka M (2014) CD166/ALCAM expression is characteristic of tumorigenicity and invasive and migratory activities of pancreatic cancer cells. PLoS One 9:e107247

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Genkinger JM, Spiegelman D, Anderson KE, Bernstein L, van den Brandt PA, Calle EE, English DR, Folsom AR, Freudenheim JL, Fuchs CS, Giles GG, Giovannucci E, Horn-Ross PL, Larsson SC, Leitzmann M, Mannisto S, Marshall JR, Miller AB, Patel AV, Rohan TE, Stolzenberg-Solomon RZ, Verhage BA, Virtamo J, Willcox BJ, Wolk A, Ziegler RG, Smith-Warner SA (2011) A pooled analysis of 14 cohort studies of anthropometric factors and pancreatic cancer risk. Int J Cancer 129:1708–1717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Giannakis M, Stappenbeck TS, Mills JC, Leip DG, Lovett M, Clifton SW, Ippolito JE, Glasscock JI, Arumugam M, Brent MR, Gordon JI (2006) Molecular properties of adult mouse gastric and intestinal epithelial progenitors in their niches. J Biol Chem 281:11292–11300

    Article  CAS  PubMed  Google Scholar 

  28. Glumac PM, LeBeau AM (2018) The role of CD133 in cancer: a concise review. Clin Transl Med 7:18–18

    Article  PubMed  PubMed Central  Google Scholar 

  29. Hashimoto O, Shimizu K, Semba S, Chiba S, Ku Y, Yokozaki H, Hori Y (2011) Hypoxia induces tumor aggressiveness and the expansion of CD133-positive cells in a hypoxia-inducible factor-1alpha-dependent manner in pancreatic cancer cells. Pathobiol J Immunopathol, Mol Cell Biol 78:181–192

    Article  CAS  Google Scholar 

  30. Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ, Heeschen C (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1:313–323

    Article  CAS  PubMed  Google Scholar 

  31. Herreros-Villanueva M, Zubia-Olascoaga A, Bujanda L (2012) c-Met in pancreatic cancer stem cells: therapeutic implications. World J Gastroenterol 18:5321–5323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hsu CP, Lee LY, Hsu JT, Hsu YP, Wu YT, Wang SY, Yeh CN, Chen TC, Hwang TL (2018) CD44 predicts early recurrence in pancreatic cancer patients undergoing radical surgery. In vivo (Athens, Greece) 32:1533–1540

    CAS  Google Scholar 

  33. Huynh DL, Koh H, Chandimali N, Zhang JJ, Kim N, Kang TY, Ghosh M, Gera M, Park Y-H, Kwon T, Jeong DK (2019) BRM270 inhibits the proliferation of CD44 positive pancreatic ductal adenocarcinoma cells via downregulation of sonic hedgehog signaling. Evid Based Complement Alternat Med 2019:8

    Article  Google Scholar 

  34. Immervoll H, Hoem D, Sakariassen PØ, Steffensen OJ, Molven A (2008) Expression of the “stem cell marker” CD133 in pancreas and pancreatic ductal adenocarcinomas. BMC Cancer 8:48–48

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Ischenko I, Petrenko O, Hayman MJ (2014) Analysis of the tumor-initiating and metastatic capacity of PDX1-positive cells from the adult pancreas. Proc Natl Acad Sci U S A 111:3466–3471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ito H, Tanaka S, Akiyama Y, Shimada S, Adikrisna R, Matsumura S, Aihara A, Mitsunori Y, Ban D, Ochiai T, Kudo A, Arii S, Yamaoka S, Tanabe M (2016) Dominant expression of DCLK1 in human pancreatic cancer stem cells accelerates tumor invasion and metastasis. PLoS One 11:e0146564–e0146564

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Jaggupilli A, Elkord E (2012) Significance of CD44 and CD24 as cancer stem cell markers: an enduring ambiguity. Clin Dev Immunol 2012:708036

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Jarosz M, Sekula W, Rychlik E (2012) Influence of diet and tobacco smoking on pancreatic cancer incidence in Poland in 1960–2008. Gastroenterol Res Pract 2012:682156

    Article  PubMed  PubMed Central  Google Scholar 

  39. Jiang W, Sui X, Zhang D, Liu M, Ding M, Shi Y, Deng H (2011) CD24: a novel surface marker for PDX1-positive pancreatic progenitors derived from human embryonic stem cells. Stem Cells (Dayton, Ohio) 29:609–617

    Article  CAS  Google Scholar 

  40. Kahlert C, Weber H, Mogler C, Bergmann F, Schirmacher P, Kenngott HG, Matterne U, Mollberg N, Rahbari NN, Hinz U, Koch M, Aigner M, Weitz J (2009) Increased expression of ALCAM/CD166 in pancreatic cancer is an independent prognostic marker for poor survival and early tumour relapse. Br J Cancer 101:457–464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kim WT, Ryu CJ (2017) Cancer stem cell surface markers on normal stem cells. BMB Rep 50:285–298

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kim MP, Fleming JB, Wang H, Abbruzzese JL, Choi W, Kopetz S, McConkey DJ, Evans DB, Gallick GE (2011) ALDH activity selectively defines an enhanced tumor-initiating cell population relative to CD133 expression in human pancreatic adenocarcinoma. PLoS One 6:e20636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kiuchi S, Ikeshita S, Miyatake Y, Kasahara M (2015) Pancreatic cancer cells express CD44 variant 9 and multidrug resistance protein 1 during mitosis. Exp Mol Pathol 98:41–46

    Article  CAS  PubMed  Google Scholar 

  44. Koury J, Zhong L, Hao J (2017) Targeting signaling pathways in Cancer stem cells for Cancer treatment. Stem Cells Int 2017:10

    Article  CAS  Google Scholar 

  45. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM (2007) Identification of pancreatic cancer stem cells. Cancer Res 67:1030–1037

    Article  CAS  PubMed  Google Scholar 

  46. Li C, Lee CJ, Simeone DM (2009) Identification of human pancreatic cancer stem cells. Methods Mol Biol 568:161–173

    Article  CAS  PubMed  Google Scholar 

  47. Li C, Wu JJ, Hynes M, Dosch J, Sarkar B, Welling TH, Pasca di Magliano M, Simeone DM (2011) c-Met is a marker of pancreatic cancer stem cells and therapeutic target. Gastroenterology 141:2218–2227.e5

    Article  CAS  PubMed  Google Scholar 

  48. Li Z, Chen K, Jiang P, Zhang X, Li X, Li Z (2014) CD44v/CD44s expression patterns are associated with the survival of pancreatic carcinoma patients. Diagn Pathol 9:79

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Li X-P, Zhang X-W, Zheng L-Z, Guo W-J (2015) Expression of CD44 in pancreatic cancer and its significance. Int J Clin Exp Pathol 8:6724–6731

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Li J, Wang Y, Ge J, Li W, Yin L, Zhao Z, Liu S, Qin H, Yang J, Wang L, Ni B, Liu Y, Wang H (2018) Doublecortin-like kinase 1 (DCLK1) regulates B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1) and is associated with metastasis and prognosis in pancreatic Cancer. Cell Physiol Biochem 51:262–277

    Article  CAS  PubMed  Google Scholar 

  51. Ling X, Wu W, Fan C, Xu C, Liao J, Rich LJ, Huang R-Y, Repasky EA, Wang X, Li F (2018) An ABCG2 non-substrate anticancer agent FL118 targets drug-resistant cancer stem-like cells and overcomes treatment resistance of human pancreatic cancer. J Exp Clin Cancer Res: CR 37:240–240

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Litvinov SV, Velders MP, Bakker HA, Fleuren GJ, Warnaar SO (1994) Ep-CAM: a human epithelial antigen is a homophilic cell-cell adhesion molecule. J Cell Biol 125:437–446

    Article  CAS  PubMed  Google Scholar 

  53. Lubeseder-Martellato C, Hidalgo-Sastre A, Hartmann C, Alexandrow K, Kamyabi-Moghaddam Z, Sipos B, Wirth M, Neff F, Reichert M, Heid I, Schneider G, Braren R, Schmid RM, Siveke JT (2016) Membranous CD24 drives the epithelial phenotype of pancreatic cancer. Oncotarget 7:49156–49168

    Article  PubMed  PubMed Central  Google Scholar 

  54. Maccalli C, Volonte A, Cimminiello C, Parmiani G (2014) Immunology of cancer stem cells in solid tumours. A review. Eur J Cancer 50:649–655

    Article  CAS  PubMed  Google Scholar 

  55. Maisonneuve P, Lowenfels AB (2014) Risk factors for pancreatic cancer: a summary review of meta-analytical studies. Int J Epidemiol 44:186–198

    Article  PubMed  Google Scholar 

  56. May R, Riehl TE, Hunt C, Sureban SM, Anant S, Houchen CW (2008) Identification of a novel putative gastrointestinal stem cell and adenoma stem cell marker, doublecortin and CaM kinase-like-1, following radiation injury and in adenomatous polyposis coli/multiple intestinal neoplasia mice. Stem Cells (Dayton, Ohio) 26:630–637

    Article  Google Scholar 

  57. Meng Y, Xu B-Q, Fu Z-G, Wu B, Xu B, Chen Z-N, Li L (2015) Cytoplasmic EpCAM over-expression is associated with favorable clinical outcomes in pancreatic cancer patients with Hepatitis B virus negative infection. Int J Clin Exp Med 8:22204–22216

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Michieli P, Mazzone M, Basilico C, Cavassa S, Sottile A, Naldini L, Comoglio PM (2004) Targeting the tumor and its microenvironment by a dual-function decoy Met receptor. Cancer Cell 6:61–73

    Article  CAS  PubMed  Google Scholar 

  59. Moreb J, Schweder M, Suresh A, Zucali JR (1996) Overexpression of the human aldehyde dehydrogenase class I results in increased resistance to 4-hydroperoxycyclophosphamide. Cancer Gene Ther 3:24–30

    CAS  PubMed  Google Scholar 

  60. Noguchi K, Konno M, Eguchi H, Kawamoto K, Mukai R, Nishida N, Koseki J, Wada H, Akita H, Satoh T, Marubashi S, Nagano H, Doki Y, Mori M, Ishii H (2018) c-Met affects gemcitabine resistance during carcinogenesis in a mouse model of pancreatic cancer. Oncol Lett 16:1892–1898

    PubMed  PubMed Central  Google Scholar 

  61. Nomura A, Banerjee S, Chugh R, Dudeja V, Yamamoto M, Vickers SM, Saluja AK (2015) CD133 initiates tumors, induces epithelial-mesenchymal transition and increases metastasis in pancreatic cancer. Oncotarget 6:8313–8322

    Article  PubMed  PubMed Central  Google Scholar 

  62. Ohara Y, Oda T, Sugano M, Hashimoto S, Enomoto T, Yamada K, Akashi Y, Miyamoto R, Kobayashi A, Fukunaga K, Morishita Y, Ohkohchi N (2013) Histological and prognostic importance of CD44(+) /CD24(+) /EpCAM(+) expression in clinical pancreatic cancer. Cancer Sci 104:1127–1134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Pan WL, Wang Y, Hao Y, Wong JH, Chan WC, Wan DC, Ng TB (2018) Overexpression of CXCR4 synergizes with LL-37 in the metastasis of breast cancer cells. Biochim Biophys Acta Mol basis Dis 1864:3837–3846

    Article  CAS  PubMed  Google Scholar 

  64. Patriarca C, Macchi RM, Marschner AK, Mellstedt H (2012) Epithelial cell adhesion molecule expression (CD326) in cancer: a short review. Cancer Treat Rev 38:68–75

    Article  CAS  PubMed  Google Scholar 

  65. Pothula SP, Xu Z, Goldstein D, Biankin AV, Pirola RC, Wilson JS, Apte MV (2016) Hepatocyte growth factor inhibition: a novel therapeutic approach in pancreatic cancer. Br J Cancer 114:269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Prasetyanti PR, Medema JP (2017) Intra-tumor heterogeneity from a cancer stem cell perspective. Mol Cancer 16:41–41

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Rall CJ, Rustgi AK (1995) CD44 isoform expression in primary and metastatic pancreatic adenocarcinoma. Cancer Res 55:1831–1835

    CAS  PubMed  Google Scholar 

  68. Rasheed ZA, Yang J, Wang Q, Kowalski J, Freed I, Murter C, Hong SM, Koorstra JB, Rajeshkumar NV, He X, Goggins M, Iacobuzio-Donahue C, Berman DM, Laheru D, Jimeno A, Hidalgo M, Maitra A, Matsui W (2010) Prognostic significance of tumorigenic cells with mesenchymal features in pancreatic adenocarcinoma. J Natl Cancer Inst 102:340–351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Rawla P, Sunkara T, Gaduputi V (2019) Epidemiology of pancreatic cancer: global trends, etiology and risk factors. World J Oncol 10:10–27

    Article  PubMed  PubMed Central  Google Scholar 

  70. Sakaue T, Koga H, Iwamoto H, Nakamura T, Ikezono Y, Abe M, Wada F, Masuda A, Tanaka T, Fukahori M, Ushijima T, Mihara Y, Naitou Y, Okabe Y, Kakuma T, Ohta K, Nakamura KI, Torimura T (2019) Glycosylation of ascites-derived exosomal CD133: a potential prognostic biomarker in patients with advanced pancreatic cancer. Med Mol Morphol. https://doi.org/10.1007/s00795-019-00218-5

    Article  PubMed  CAS  Google Scholar 

  71. Salaria S, Means A, Revetta F, Idrees K, Liu E, Shi C (2015) Expression of CD24, a stem cell marker, in pancreatic and small intestinal neuroendocrine tumors. Am J Clin Pathol 144:642–648

    Article  CAS  PubMed  Google Scholar 

  72. Saur D, Seidler B, Schneider G, Algul H, Beck R, Senekowitsch-Schmidtke R, Schwaiger M, Schmid RM (2005) CXCR4 expression increases liver and lung metastasis in a mouse model of pancreatic cancer. Gastroenterology 129:1237–1250

    Article  CAS  PubMed  Google Scholar 

  73. Shakir M, Tang D, Zeh HJ, Tang SW, Anderson CJ, Bahary N, Lotze MT (2015) The chemokine receptors CXCR4/CXCR7 and their primary heterodimeric ligands CXCL12 and CXCL12/high mobility group box 1 in pancreatic cancer growth and development: finding flow. Pancreas 44:528–534

    Article  CAS  PubMed  Google Scholar 

  74. Singh S, Srivastava SK, Bhardwaj A, Owen LB, Singh AP (2010) CXCL12-CXCR4 signalling axis confers gemcitabine resistance to pancreatic cancer cells: a novel target for therapy. Br J Cancer 103:1671–1679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Singh S, Arcaroli JJ, Orlicky DJ, Chen Y, Messersmith WA, Bagby S, Purkey A, Quackenbush KS, Thompson DC, Vasiliou V (2016) Aldehyde dehydrogenase 1B1 as a modulator of pancreatic adenocarcinoma. Pancreas 45:117–122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Sobek KM, Cummings JL, Bacich DJ, O’Keefe DS (2017) Contrasting roles of the ABCG2 Q141K variant in prostate cancer. Exp Cell Res 354:40–47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Sugahara KN, Hirata T, Hayasaka H, Stern R, Murai T, Miyasaka M (2006) Tumor cells enhance their own CD44 cleavage and motility by generating hyaluronan fragments. J Biol Chem 281:5861–5868

    Article  CAS  PubMed  Google Scholar 

  78. Suzuki A, Nakauchi H, Taniguchi H (2004) Prospective isolation of multipotent pancreatic progenitors using flow-cytometric cell sorting. Diabetes 53:2143–2152

    Article  CAS  PubMed  Google Scholar 

  79. Tachezy M, Zander H, Marx AH, Stahl PR, Gebauer F, Izbicki JR, Bockhorn M (2012) ALCAM (CD166) expression and serum levels in pancreatic cancer. PLoS One 7:e39018–e39018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Tirino V, Desiderio V, Paino F, De Rosa A, Papaccio F, La Noce M, Laino L, De Francesco F, Papaccio G (2013) Cancer stem cells in solid tumors: an overview and new approaches for their isolation and characterization. FASEB J 27:13–24

    Article  CAS  PubMed  Google Scholar 

  81. Todaro M, Francipane MG, Medema JP, Stassi G (2010) Colon cancer stem cells: promise of targeted therapy. Gastroenterology 138:2151–2162

    Article  CAS  PubMed  Google Scholar 

  82. Tomita H, Tanaka K, Tanaka T, Hara A (2016) Aldehyde dehydrogenase 1A1 in stem cells and cancer. Oncotarget 7:11018–11032

    Article  PubMed  PubMed Central  Google Scholar 

  83. Trzpis M, McLaughlin PMJ, de Leij LMFH, Harmsen MC (2007) Epithelial cell adhesion molecule: more than a carcinoma marker and adhesion molecule. Am J Pathol 171:386–395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Ulasov IV, Nandi S, Dey M, Sonabend AM, Lesniak MS (2011) Inhibition of sonic hedgehog and notch pathways enhances sensitivity of CD133(+) glioma stem cells to temozolomide therapy. Mol Med (Cambridge, Mass.) 17:103–112

    CAS  Google Scholar 

  85. van der Gun BT, Melchers LJ, Ruiters MH, de Leij LF, McLaughlin PM, Rots MG (2010) EpCAM in carcinogenesis: the good, the bad or the ugly. Carcinogenesis 31:1913–1921

    Article  PubMed  CAS  Google Scholar 

  86. Vander Linden C, Corbet C (2019) Therapeutic targeting of cancer stem cells: integrating and exploiting the acidic niche. Front Oncol 9:159

    Article  PubMed  PubMed Central  Google Scholar 

  87. Vassalli G (2019) Aldehyde dehydrogenases: not just markers, but functional regulators of stem cells. Stem Cells Int 2019:15

    Article  CAS  Google Scholar 

  88. Wang J, Xin B, Wang H, He X, Wei W, Zhang T, Shen X (2016) Gastrin regulates ABCG2 to promote the migration, invasion and side populations in pancreatic cancer cells via activation of NF-kappaB signaling. Exp Cell Res 346:74–84

    Article  CAS  PubMed  Google Scholar 

  89. Wang X, Cao Y, Zhang S, Chen Z, Fan L, Shen X, Zhou S, Chen D (2017) Stem cell autocrine CXCL12/CXCR4 stimulates invasion and metastasis of esophageal cancer. Oncotarget 8:36149–36160

    Article  PubMed  PubMed Central  Google Scholar 

  90. Wang RQ, Geng J, Sheng WJ, Liu XJ, Jiang M, Zhen YS (2019) The ionophore antibiotic gramicidin A inhibits pancreatic cancer stem cells associated with CD47 down-regulation. Cancer Cell Int 19:145

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Westover D, Li F (2015) New trends for overcoming ABCG2/BCRP-mediated resistance to cancer therapies. J Exp Clin Cancer Res: CR 34:159

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Yamamoto T, Yagi S, Kinoshita H, Sakamoto Y, Okada K, Uryuhara K, Morimoto T, Kaihara S, Hosotani R (2015) Long-term survival after resection of pancreatic cancer: a single-center retrospective analysis. World J Gastroenterol 21:262–268

    Article  PubMed  PubMed Central  Google Scholar 

  93. Yan B, Jiang Z, Cheng L, Chen K, Zhou C, Sun L, Qian W, Li J, Cao J, Xu Q, Ma Q, Lei J (2018) Paracrine HGF/c-MET enhances the stem cell-like potential and glycolysis of pancreatic cancer cells via activation of YAP/HIF-1α. Exp Cell Res 371:63–71

    Article  CAS  PubMed  Google Scholar 

  94. Yuan Y, Yang Z, Miao X, Li D, Liu Z, Zou Q (2015) The clinical significance of FRAT1 and ABCG2 expression in pancreatic ductal adenocarcinoma. Tumour Biol 36:9961–9968

    Article  CAS  PubMed  Google Scholar 

  95. Zhan T, Rindtorff N, Boutros M (2017) Wnt signaling in cancer. Oncogene 36:1461–1473

    Article  CAS  PubMed  Google Scholar 

  96. Zhao D, Mo Y, Li MT, Zou SW, Cheng ZL, Sun YP, Xiong Y, Guan KL, Lei QY (2014) NOTCH-induced aldehyde dehydrogenase 1A1 deacetylation promotes breast cancer stem cells. J Clin Invest 124:5453–5465

    Article  PubMed  PubMed Central  Google Scholar 

  97. Zhao S, Chen C, Chang K, Karnad A, Jagirdar J, Kumar AP, Freeman JW (2016) CD44 expression level and isoform contributes to pancreatic Cancer cell plasticity, invasiveness, and response to therapy. Clin Cancer Res 22:5592–5604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Zhou B, Sun C, Hu X, Zhan H, Zou H, Feng Y, Qiu F, Zhang S, Wu L, Zhang B (2017) MicroRNA-195 suppresses the progression of pancreatic cancer by targeting DCLK1. Cell Physiol Biochem 44:1867–1881

    Article  CAS  PubMed  Google Scholar 

  99. Zhu L, Finkelstein D, Gao C, Shi L, Wang Y, Lopez-Terrada D, Wang K, Utley S, Pounds S, Neale G, Ellison D, Onar-Thomas A, Gilbertson RJ (2016) Multi-organ mapping of cancer risk. Cell 166:1132–1146.e7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Conflict of Interest

There are no conflicts of interests.

Author information

Authors and Affiliations

  1. Department of Zoology, Visvodaya Government Degree College, Venkatagiri, India

    L. Saikrishna

  2. Dr. LV Prasad Diagnostics and Research Laboratory, Hyderabad, Telangana, India

    Prameswari Kasa

  3. Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Saimila Momin

  4. Guru Ghasidas Vishwavidyalaya, Bilaspur, India

    L. V. K. S. Bhaskar

Authors
  1. L. Saikrishna
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Prameswari Kasa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Saimila Momin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. V. K. S. Bhaskar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. V. K. S. Bhaskar .

Editor information

Editors and Affiliations

  1. Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA

    Ganji Purnachandra Nagaraju

  2. Department of Animal Biology, University of Hyderabad, Hyderabad, Telangana, India

    Aramati BM Reddy

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Saikrishna, L., Kasa, P., Momin, S., Bhaskar, L.V.K.S. (2019). Perspectives and Molecular Understanding of Pancreatic Cancer Stem Cells. In: Nagaraju, G., BM Reddy, A. (eds) Exploring Pancreatic Metabolism and Malignancy. Springer, Singapore. https://doi.org/10.1007/978-981-32-9393-9_9

Download citation

Publish with us

Policies and ethics

Search

Navigation