Advertisement

Cellular Oncology

, Volume 42, Issue 6, pp 727–738 | Cite as

The therapeutic potential of mesenchymal stem cells in lung cancer: benefits, risks and challenges

  • Lourdes Cortes-DericksEmail author
  • Domenico Galetta
Review
First Online:

Abstract

Background

Lung cancer is one of the most challenging diseases to treat. In the past decades standard therapy including surgery, chemo- and radiation therapy, alone or in combination has not changed the high mortality rate and poor prognosis. In recent years, mesenchymal stem cells (MSCs) have emerged as putative therapeutic tools due to their intrinsic tumor tropism, anti-tumor and immunoregulatory properties. MSCs release biomolecules that are thought to exert the same beneficial effects as their cellular counterparts and, as such, they may offer practical possibilities of using MSC-secreted products. Owing to their innate affinity to home to tumor sites, MSCs have also gained interest as selective vehicles for the delivery of anti-cancer agents. However, MSCs are also known to confer pro-oncogenic effects, rendering them into double-sword weapons against neoplastic diseases.

Conclusions

Here, we present published data on the cell- and secretome-based therapeutic competences of MSCs, as well as on their potential as engineered delivery vectors for the treatment of lung cancer. Despite the controversial role of MSCs in the context of lung cancer therapy, current findings support hopeful perspectives to harness the potential of MSC-based regimens that may augment current treatment modalities in lung cancer.

Keywords

Lung cancer Lung cancer therapy Mesenchymal stem cells Mesenchymal stem cell secretome Anti−/pro-tumorigenic effect 

Abbreviations

hBMMSCs

human bone marrow mesenchymal stem cells

BMMSC-CM

bone marrow mesenchymal stem cell-conditioned medium

hMSCs

human mesenchymal stem cells

hUCMSCs

human umbilical cord mesenchymal stem cells

hLMSC-CM

human lung mesenchymal stem cell-conditioned medium

hLcMSCs

human lung cancer-derived mesenchymal stem cells

hAMSCs

human adipose tissue-derived mesenchymal stem cells

AMSCs

adipose-derived mesenchymal stem cells

OSM

oncostatin M

elF4G1

eukaryotic translation initiation factor 4 gamma 1

elF4E

eukaryotic translation initiation factor 4E

AKT

protein kinase B

PI3K

phosphoinositide 3-kinase

STAT3

signal transducer and activator of transcription 3

TOR

target of rapamycin

NSCLC

non-small cell lung cancer cell

LLC

Lewis lung cancer (mouse)

AC

adenocarcinoma TSA-Lu + luciferase-positive mouse adenocarcinoma cells.

AREG

amphiregulin

IL-6

interleukin 2

JAK2

Janus kinase 2

STAT3

signal transducer and activator of transcription protein 3

NK

natural killer cell

ROS

reactive oxygen species

EMT

epithelial-mesenchymal transition

IFN- γ

interferon gamma

AREG

amphiregulin

DOX

doxorubicin

IL-12

interleukin 12

IL-24

interleukin 24

IFN-β

interferon beta

IFN- γ

interferon gamma

PEDF

pigment epithelium-derived factor

PTX

paclitaxel

TRAIL

TNF-related apoptosis- inducing ligand

CDA/UPRT

cytosine deaminase-uracil phosphoribosyltransferase protein

Ad.TRAIL

adenoviral vector-expressing TRAIL

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

Notes

Acknowledgements

We thank Prof. Dr. Stefan Kirschner for his continuous moral support.

Author’s contribution

LCD and DG contributed equally in the conception, organization of data and writing of the manuscript. All authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

References

  1. 1.
    F.R. Hirsch, G.V. Scagliotti, J.L. Mulshine, R. Kwon, W.J. Curran, Y.-L. Wu, L. Paz-Ares, Lung cancer: Current therapies and new targeted treatments. Lancet 389, 299–311 (2017).  https://doi.org/10.1016/S0140-6736(16)30958-8 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    R.S. Herbst, J.V. Heymach, S.M. Lippman, Lung Cancer. N Engl J Med 359, 1367–1380 (2008).  https://doi.org/10.1056/NEJMra0802714 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    C.-L. Zhang, T. Huang, B.-L. Wu, W.-X. He, D. Liu, Stem cells in cancer therapy: Opportunities and challenges. Oncotarget 8, 75756–75766 (2017).  https://doi.org/10.18632/oncotarget.20798 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    A.J. Friedenstein, K.V. Petrakova, A.I. Kurolesova, G.P. Frolova, Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 6, 230–247 (1968)CrossRefGoogle Scholar
  5. 5.
    A. Erices, P. Conget, J.J. Minguell, Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol 109, 235–242 (2000)CrossRefGoogle Scholar
  6. 6.
    S. Gronthos, D.M. Franklin, H.A. Leddy, P.G. Robey, R.W. Storms, J.M. Gimble, Surface protein characterization of human adipose tissue-derived stromal cells. J Cell Physiol 189, 54–63 (2001)CrossRefGoogle Scholar
  7. 7.
    C. Campagnoli, I.A. Roberts, S. Kumar, P.R. Bennett, I. Bellantuono, N.M. Fisk, Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood 98, 2396–2402 (2001)CrossRefGoogle Scholar
  8. 8.
    M.-S. Tsai, J.-L. Lee, Y.-J. Chang, S.-M. Hwang, Isolation of human multipotent mesenchymal stem cells from second-trimester amniotic fluid using a novel two-stage culture protocol. Hum Reprod Oxf Engl 19, 1450–1456 (2004).  https://doi.org/10.1093/humrep/deh279 CrossRefGoogle Scholar
  9. 9.
    K. Igura, X. Zhang, K. Takahashi, A. Mitsuru, S. Yamaguchi, T.A. Takashi, Isolation and characterization of mesenchymal progenitor cells from chorionic villi of human placenta. Cytotherapy 6, 543–553 (2004)CrossRefGoogle Scholar
  10. 10.
    N.J. Zvaifler, L. Marinova-Mutafchieva, G. Adams, C.J. Edwards, J. Moss, J.A. Burger, R.N. Maini, Mesenchymal precursor cells in the blood of normal individuals. Arthritis Res 2, 477–488 (2000)CrossRefGoogle Scholar
  11. 11.
    M. Dominici, K. Le Blanc, I. Mueller, I. Slaper-Cortenbach, F. Marini, D. Krause, R. Deans, A. Keating, D.J. Prockop, E. Horwitz, Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8, 315–317 (2006)CrossRefGoogle Scholar
  12. 12.
    F.J. Vizoso, N. Eiro, S. Cid, J. Schneider, R. Perez-Fernandez, Mesenchymal stem cell Secretome: Toward cell-free therapeutic strategies in regenerative medicine. Int J Mol Sci 18 (2017).  https://doi.org/10.3390/ijms18091852 CrossRefGoogle Scholar
  13. 13.
    S.H. Ranganath, O. Levy, M.S. Inamdar, J.M. Karp, Harnessing the Mesenchymal stem cell Secretome for the treatment of cardiovascular disease. Cell Stem Cell 10, 244–258 (2012).  https://doi.org/10.1016/j.stem.2012.02.005 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    L. Li, H. Tian, Z. Chen, W. Yue, S. Li, W. Li, Inhibition of lung cancer cell proliferation mediated by human mesenchymal stem cells. Acta Biochim Biophys Sin 43, 143–148 (2011).  https://doi.org/10.1093/abbs/gmq118 CrossRefPubMedGoogle Scholar
  15. 15.
    A.Y. Khakoo, S. Pati, S.A. Anderson, W. Reid, M.F. Elshal, I.I. Rovira, A.T. Nguyen, D. Malide, C.A. Combs, G. Hall, J. Zhang, M. Raffeld, T.B. Rogers, W. Stetler-Stevenson, J.A. Frank, M. Reitz, T. Finkel, Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi’s sarcoma. J Exp Med 203, 1235–1247 (2006).  https://doi.org/10.1084/jem.20051921 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    K. Gauthaman, F.C. Yee, S. Cheyyatraivendran, A. Biswas, M. Choolani, A. Bongso, Human umbilical cord Wharton’s jelly stem cell (hWJSC) extracts inhibit cancer cell growth in vitro. J Cell Biochem 113, 2027–2039 (2012).  https://doi.org/10.1002/jcb.24073 CrossRefPubMedGoogle Scholar
  17. 17.
    L. Cortes-Dericks, L. Froment, G. Kocher, R.A. Schmid, Human lung-derived mesenchymal stem cell-conditioned medium exerts in vitro antitumor effects in malignant pleural mesothelioma cell lines. Stem Cell Res Ther 7, 25 (2016).  https://doi.org/10.1186/s13287-016-0282-7 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    J.-O. Ahn, Y.-R. Coh, H.-W. Lee, I.-S. Shin, S.-K. Kang, H.-Y. Youn, Human adipose tissue-derived mesenchymal stem cells inhibit melanoma growth in vitro and in vivo. Anticancer Res 35, 159–168 (2015)PubMedGoogle Scholar
  19. 19.
    G. Lazennec, C. Jorgensen, Concise review: Adult multipotent stromal cells and cancer: Risk or benefit? Stem Cells 26, 1387–1394 (2008).  https://doi.org/10.1634/stemcells.2007-1006 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    R. Ramasamy, Lam EW-F, Soeiro I, Tisato V, bonnet D, Dazzi , Mesenchymal stem cells inhibit proliferation and apoptosis of tumor cells: Impact on in vivo tumor growth. Leukemia 21, 304–310 (2007)CrossRefGoogle Scholar
  21. 21.
    X. Zhao, X. Wu, M. Qian, Y. Song, D. Wu, W. Zhang, Knockdown of TGF-β1 expression in human umbilical cord mesenchymal stem cells reverts their exosome-mediated EMT promoting effect on lung cancer cells. Cancer Lett 428, 34–44 (2018).  https://doi.org/10.1016/j.canlet.2018.04.026 CrossRefPubMedGoogle Scholar
  22. 22.
    F. Vulcano, L. Milazzo, C. Ciccarelli, A. Eramo, G. Sette, A. Mauro, G. Macioce, A. Martinelli, R. La Torre, P. Casalbore, H.J. Hassan, A. Giampaolo, Wharton’s jelly mesenchymal stromal cells have contrasting effects on proliferation and phenotype of cancer stem cells from different subtypes of lung cancer. Exp Cell Res 345, 190–198 (2016).  https://doi.org/10.1016/j.yexcr.2016.06.003 CrossRefPubMedGoogle Scholar
  23. 23.
    L.L.H. Tian, W. Yue, F. Zhu, S. Li, W. Li, Human mesenchymal stem cells play a dual role on tumor cell growth in vitro and in vivo. J Cell Physiol 226, 1860–1867 (2011).  https://doi.org/10.1002/jcp.22511 CrossRefPubMedGoogle Scholar
  24. 24.
    J.J. Rhyu, J.-W. Yun, E. Kwon, J.-H. Che, B.-C. Kang, Dual effects of human adipose tissue-derived mesenchymal stem cells in human lung adenocarcinoma A549 xenografts and colorectal adenocarcinoma HT-29 xenografts in mice. Oncol Rep 34, 1733–1744 (2015).  https://doi.org/10.3892/or.2015.4185 CrossRefPubMedGoogle Scholar
  25. 25.
    G.J. Maestroni, E. Hertens, P. Galli, Factor(s) from nonmacrophage bone marrow stromal cells inhibit Lewis lung carcinoma and B16 melanoma growth in mice. Cell Mol Life Sci CMLS 55, 663–667 (1999)CrossRefGoogle Scholar
  26. 26.
    M.-L. Wang, C.-M. Pan, S.-H. Chiou, W.-H. Chen, H.-Y. Chang, O.K.-S. Lee, H.S. Hsu, C.W. Wu, Oncostatin m modulates the mesenchymal-epithelial transition of lung adenocarcinoma cells by a mesenchymal stem cell-mediated paracrine effect. Cancer Res 72, 6051–6064 (2012).  https://doi.org/10.1158/0008-5472.CAN-12-1568 CrossRefPubMedGoogle Scholar
  27. 27.
    O. Attar-Schneider, V. Zismanov, L. Drucker, M. Gottfried, Secretome of human bone marrow mesenchymal stem cells: An emerging player in lung cancer progression and mechanisms of translation initiation. Tumor Biol 37, 4755–4765 (2016).  https://doi.org/10.1007/s13277-015-4304-3 CrossRefGoogle Scholar
  28. 28.
    M. Pan, L. Hou, J. Zhang, D. Zhao, J. Hua, Z. Wang, J. He, H. Jiang, H. Hu, L. Zhang, Inhibitory effect and molecular mechanism of mesenchymal stem cells on NSCLC cells. Mol Cell Biochem 441, 63–76 (2017).  https://doi.org/10.1007/s11010-017-3174-y CrossRefPubMedGoogle Scholar
  29. 29.
    L. Chai, L. Bai, L. Li, F. Chen, J. Zhang, Biological functions of lung cancer cells are suppressed in co-culture with mesenchymal stem cells isolated from umbilical cord. Exp Ther Med 15, 1076–1080 (2018).  https://doi.org/10.3892/etm.2017.5456 CrossRefPubMedGoogle Scholar
  30. 30.
    M. Kéramidas, F. de Fraipont, A. Karageorgis, A. Moisan, V. Persoons, M.-J. Richard, J.L. Coll, C. Rome, The dual effect of mscs on tumour growth and tumour angiogenesis. Stem Cell Res Ther 4, 41 (2013).  https://doi.org/10.1186/scrt195 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    T. Liu, K. Zhu, C. Ke, S. Yang, F. Yang, Z. Li, Z. Zhang, Mesenchymal stem cells inhibited development of lung cancer induced by chemical carcinogens in a rat model. Am J Transl Res 9, 2891–2900 (2017)PubMedPubMedCentralGoogle Scholar
  32. 32.
    P.Y. Jung, H. Ryu, K.-J. Rhee, S. Hwang, C.G. Lee, S.-Y. Gwon, J. Kim, B.-S. Yoo, S.-K. Baik, K.-S. Bae, Y.-W. Eom, Adipose tissue-derived mesenchymal stem cells cultured at high density express IFN-β and TRAIL and suppress the growth of H460 human lung cancer cells. Cancer Lett 440, 202–441, 210 (2019).  https://doi.org/10.1016/j.canlet.2018.10.017 CrossRefGoogle Scholar
  33. 33.
    H.-J. Wei, W.-C. Lo, J.A. Nickoloff, W.-H. Chen, H.-Y. Liu, Y.-T. Chang, P.-C. Yang, C.-W. Wu, D.F. Williams, J.G. Gelovani, W.-P. Deng, FOXF1 mediates mesenchymal stem cell fusion-induced reprogramming of lung cancer cells. Oncotarget 5, 9514–9529 (2014).  https://doi.org/10.18632/oncotarget.2413 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    J.F. Modiano, B.A. Lindborg, R.T. McElmurry, M. Lewellen, C.L. Forster, E.A. Zamora, J. Schaack, D. Bellgrau, O’Brien TD, Tolar J, Mesenchymal stromal cells inhibit murine syngeneic anti-tumor immune responses by attenuating inflammation and reorganizing the tumor microenvironment. Cancer Immunol Immunother 64, 1449–1460 (2015).  https://doi.org/10.1007/s00262-015-1749-6 CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    M. Gazdic, B. Simovic Markovic, N. Jovicic, M. Misirkic-Marjanovic, V. Djonov, V. Jakovljevic, N. Arsenijevic, M.L. Lukic, V. Volarevic, Mesenchymal stem cells promote metastasis of lung cancer cells by downregulating systemic antitumor immune response. Stem Cells Int 2017, 1–11 (2017).  https://doi.org/10.1155/2017/6294717 CrossRefGoogle Scholar
  36. 36.
    O. Carnet, J. Lecomte, A. Masset, I. Primac, T. Durré, L. Maertens, B. Detry, S. Blacher, C. Gilles, C. Pequeux, J. Paupert, J.M. Foidart, G. Jerusalem, D. Cataldo, A. Noel, Mesenchymal stem cells shed Amphiregulin at the surface of lung carcinoma cells in a Juxtacrine manner. Neoplasia 17, 552–563 (2015).  https://doi.org/10.1016/j.neo.2015.07.002 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    J.-H. Lu, H.-J. Wei, B.-Y. Peng, H.-H. Chou, W.-H. Chen, H.-Y. Liu, W.-P. Deng, Adipose-derived stem cells enhance Cancer stem cell property and tumor formation capacity in Lewis lung carcinoma cells through an Interleukin-6 paracrine circuit. Stem Cells Dev 25, 1833–1842 (2016).  https://doi.org/10.1089/scd.2016.0163 CrossRefPubMedGoogle Scholar
  38. 38.
    H.-S. Hsu, J.-H. Lin, T.-W. Hsu, K. Su, C.-W. Wang, K.-Y. Yang, S.-H. Chiou, S.-C. Hung, Mesenchymal stem cells enhance lung cancer initiation through activation of IL-6/JAK2/STAT3 pathway. Lung Cancer Amst Neth 75, 167–177 (2012).  https://doi.org/10.1016/j.lungcan.2011.07.001 CrossRefGoogle Scholar
  39. 39.
    D. Luo, S. Hu, C. Tang, G. Liu, Mesenchymal stem cells promote cell invasion and migration and autophagy-induced epithelial-mesenchymal transition in A549 lung adenocarcinoma cells. Cell Biochem Funct 36, 88–94 (2018).  https://doi.org/10.1002/cbf.3320 CrossRefPubMedGoogle Scholar
  40. 40.
    S. Ohkouchi, G.J. Block, A.M. Katsha, M. Kanehira, M. Ebina, T. Kikuchi, Y. Saijo, T. Nukiwa, D.J. Prockop, Mesenchymal stromal cells protect cancer cells from ROS-induced apoptosis and enhance the Warburg effect by secreting STC1. Mol Ther J Am Soc Gene Ther 20, 417–423 (2012).  https://doi.org/10.1038/mt.2011.259 CrossRefGoogle Scholar
  41. 41.
    Y.M. Park, S.H. Yoo, S.-H. Kim, Adipose-derived stem cells induced EMT-like changes in H358 lung cancer cells. Anticancer Res 33, 4421–4430 (2013)PubMedGoogle Scholar
  42. 42.
    L. Ampollini, D. Madeddu, A. Falco, C. Frati, B. Lorusso, G. Graiani, F. Saccani, A. Gervasi, P. Rossetti, S. Bonomini, L. Gnetti, C.A. Lagrasta, E.M. Silini, E. Quaini, P. Petronini, R. Alfieri, M. Rusca, P. Carbognani, F. Quaini, Lung mesenchymal cells function as an inductive microenvironment for human lung cancer propagating cells†. Eur J Cardiothorac Surg 46, e103–e112 (2014).  https://doi.org/10.1093/ejcts/ezu359 CrossRefPubMedGoogle Scholar
  43. 43.
    S.C. Heo, K.O. Lee, S.H. Shin, Y.W. Kwon, Y.M. Kim, C.H. Lee, Y.D. Kim, M.K. Lee, J.H. Kim, Periostin mediates human adipose tissue-derived mesenchymal stem cell-stimulated tumor growth in a xenograft lung adenocarcinoma model. Biochim Biophys Acta 1813, 2061–2070 (2011).  https://doi.org/10.1016/j.bbamcr.2011.08.004 CrossRefPubMedGoogle Scholar
  44. 44.
    O. Attar-Schneider, L. Drucker, M. Gottfried, The effect of mesenchymal stem cells’ secretome on lung cancer progression is contingent on their origin: Primary or metastatic niche. Lab Investig 98, 1549–1561 (2018).  https://doi.org/10.1038/s41374-018-0110-z CrossRefPubMedGoogle Scholar
  45. 45.
    M. Studeny, F.C. Marini, R.E. Champlin, C. Zompetta, I.J. Fidler, M. Andreeff, Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors. Cancer Res 62, 3603–3608 (2002)PubMedGoogle Scholar
  46. 46.
    E.K. Sage, R.M. Thakrar, S.M. Janes, Genetically modified mesenchymal stromal cells in cancer therapy. Cytotherapy 18, 1435–1445 (2016).  https://doi.org/10.1016/j.jcyt.2016.09.003 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    K. Le Blanc, O. Ringdén, Immunobiology of human mesenchymal stem cells and future use in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 11, 321–334 (2005).  https://doi.org/10.1016/j.bbmt.2005.01.005 CrossRefGoogle Scholar
  48. 48.
    I.T. Cavarretta, V. Altanerova, M. Matuskova, L. Kucerova, Z. Culig, C. Altaner, Adipose tissue–derived Mesenchymal stem cells expressing Prodrug-converting enzyme inhibit human prostate tumor growth. Mol Ther 18, 223–231 (2010).  https://doi.org/10.1038/mt.2009.23 CrossRefPubMedGoogle Scholar
  49. 49.
    A.I. Caplan, S.P. Bruder, Mesenchymal stem cells: Building blocks for molecular medicine in the 21st century. Trends Mol Med 7, 259–264 (2001)CrossRefGoogle Scholar
  50. 50.
    T. Sadhukha, T.D. O’Brien, S. Prabha, Nano-engineered mesenchymal stem cells as targeted therapeutic carriers. J Control Release 196, 243–251 (2014).  https://doi.org/10.1016/j.jconrel.2014.10.015 CrossRefPubMedGoogle Scholar
  51. 51.
    B. Layek, T. Sadhukha, J. Panyam, S. Prabha, Nano-engineered Mesenchymal stem cells increase therapeutic efficacy of anticancer drug through true active tumor targeting. Mol Cancer Ther 17, 1196–1206 (2018).  https://doi.org/10.1158/1535-7163.MCT-17-0682 CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    F. Petrella, V. Coccè, C. Masia, M. Milani, E.O. Salè, G. Alessandri, E. Parati, F. Sisto, F. Pentimalli, A.T. Brini, A. Pessina, L. Spaggiari, Paclitaxel-releasing mesenchymal stromal cells inhibit in vitro proliferation of human mesothelioma cells. Biomed Pharmacother 87, 755–758 (2017).  https://doi.org/10.1016/j.biopha.2017.01.118 CrossRefPubMedGoogle Scholar
  53. 53.
    S. Yao, X. Li, J. Liu, Y. Sun, Z. Wang, Y. Jiang, Maximized nanodrug-loaded mesenchymal stem cells by a dual drug-loaded mode for the systemic treatment of metastatic lung cancer. Drug Deliv 24, 1372–1383 (2017).  https://doi.org/10.1080/10717544.2017.1375580 CrossRefPubMedGoogle Scholar
  54. 54.
    X. Li, P. Zhang, X. Liu, P. Lv, Expression of interleukin-12 by adipose-derived mesenchymal stem cells for treatment of lung adenocarcinoma. Thorac Cancer 6, 80–84 (2015)CrossRefGoogle Scholar
  55. 55.
    X. Zhang, L. Zhang, W. Xu, H. Qian, S. Ye, W. Zhu, H. Cao, Y. Yan, W. Li, M. Wang, W. Wang, R. Zhang, Experimental therapy for lung cancer: Umbilical cord-derived mesenchymal stem cell-mediated interleukin-24 delivery. Curr Cancer Drug Targets 13, 92–102 (2013)CrossRefGoogle Scholar
  56. 56.
    M. MacFarlane, TRAIL-induced signalling and apoptosis. Toxicol Lett 139, 89–97 (2003)CrossRefGoogle Scholar
  57. 57.
    A. Mohr, M. Lyons, L. Deedigan, T. Harte, G. Shaw, L. Howard, F. Barry, O’Brien T, Zwacka R, Mesenchymal stem cells expressing TRAIL lead to tumour growth inhibition in an experimental lung cancer model. J Cell Mol Med 12, 2628–2643 (2008).  https://doi.org/10.1111/j.1582-4934.2008.00317.x CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    M.R. Loebinger, A. Eddaoudi, D. Davies, S.M. Janes, Mesenchymal stem cell delivery of TRAIL can eliminate metastatic cancer. Cancer Res 69, 4134–4142 (2009).  https://doi.org/10.1158/0008-5472.CAN-08-4698 CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    X. Yang, J. Du, X. Xu, C. Xu, W. Song, IFN-γ-secreting-Mesenchymal stem cells exert an antitumor effect in vivo via the TRAIL pathway. J Immunol Res 2014, 1–9 (2014).  https://doi.org/10.1155/2014/318098 CrossRefGoogle Scholar
  60. 60.
    L.S. Krassikova, S.S. Karshieva, I.B. Cheglakov, A.V. Belyavsky, Combined treatment, based on lysomustine administration with mesenchymal stem cells expressing cytosine deaminase therapy, leads to pronounced murine Lewis lung carcinoma growth inhibition. J Gene Med 18, 220–233 (2016).  https://doi.org/10.1002/jgm.2894 CrossRefPubMedGoogle Scholar
  61. 61.
    T. Matsuzuka, R.S. Rachakatla, C. Doi, D.K. Maurya, N. Ohta, A. Kawabata, M.M. Pyle, L. Pickel, J. Reischman, F. Marini, D. Troyer, M. Tamura, Human umbilical cord matrix-derived stem cells expressing interferon-beta gene significantly attenuate bronchioloalveolar carcinoma xenografts in SCID mice. Lung Cancer Amst Neth 70, 28–36 (2010).  https://doi.org/10.1016/j.lungcan.2010.01.003 CrossRefGoogle Scholar
  62. 62.
    Q. Chen, P. Cheng, T. Yin, H. He, L. Yang, Y. Wei, X. Chen, Therapeutic potential of bone marrow-derived mesenchymal stem cells producing pigment epithelium-derived factor in lung carcinoma. Int J Mol Med 30, 527–534 (2012).  https://doi.org/10.3892/ijmm.2012.1015 CrossRefPubMedGoogle Scholar
  63. 63.
    J. Du, Y. Zhang, C. Xu, X. Xu, Apoptin-modified human mesenchymal stem cells inhibit growth of lung carcinoma in nude mice. Mol Med Rep 12, 1023–1029 (2015).  https://doi.org/10.3892/mmr.2015.3501 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    H. Xin, M. Kanehira, H. Mizuguchi, T. Hayakawa, T. Kikuchi, T. Nukiwa, Y. Saijo, Targeted delivery of CX3CL1 to multiple lung tumors by Mesenchymal stem cells. Stem Cells 25, 1618–1626 (2007)CrossRefGoogle Scholar
  65. 65.
    D.S. Chulpanova, K.V. Kitaeva, L.G. Tazetdinova, V. James, A.A. Rizvanov, V.V. Solovyeva, Application of Mesenchymal stem cells for therapeutic agent delivery in anti-tumor treatment. Front Pharmacol 9, 259 (2018).  https://doi.org/10.3389/fphar.2018.00259
  66. 66.
    J. Luetzkendorf, L.P. Mueller, T. Mueller, H. Caysa, K. Nerger, H.-J. Schmoll, Growth inhibition of colorectal carcinoma by lentiviral TRAIL-transgenic human mesenchymal stem cells requires their substantial intratumoral presence. J Cell Mol Med 14, 2292–2304 (2010).  https://doi.org/10.1111/j.1582-4934.2009.00794.x CrossRefPubMedGoogle Scholar
  67. 67.
    L.S. Sasportas, R. Kasmieh, H. Wakimoto, S. Hingtgen, J.A.J.M. van de Water, G. Mohapatra, J.L. Figueiredo, R.L. Martuza, R. Weissleder, K. Shah, Assessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy. Proc Natl Acad Sci 106, 4822–4827 (2009).  https://doi.org/10.1073/pnas.0806647106 CrossRefPubMedGoogle Scholar
  68. 68.
    J. Galipeau, L. Sensébé, Mesenchymal stromal cells: Clinical challenges and therapeutic opportunities. Cell Stem Cell 22, 824–833 (2018).  https://doi.org/10.1016/j.stem.2018.05.004 CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    C.M.F. Gomes, The dual role of mesenchymal stem cells in tumor progression. Stem Cell Res Ther 4, 42 (2013).  https://doi.org/10.1186/scrt189 CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    W.J. Scott, J. Howington, S. Feigenberg, B. Movsas, K. Pisters, American College of Chest Physicians. Treatment of non-small cell lung cancer stage I and stage II: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 132, 234S–242S (2007).  https://doi.org/10.1378/chest.07-1378 CrossRefPubMedGoogle Scholar
  71. 71.
    D. Galetta, A. Borri, R. Gasparri, F. Petrella, L. Spaggiari, Surgical techniques and long-term results of pulmonary artery reconstruction in patients with lung Cancer. Ann Thorac Surg 100, 1196–1202 (2015).  https://doi.org/10.1016/j.athoracsur.2015.04.124 CrossRefPubMedGoogle Scholar
  72. 72.
    D. Galetta, A. Cesario, S. Margaritora, V. Porziella, A. Piraino, R.M. D’Angelillo, M.A. Gambacorta, S. Ramella, S. Trodella, S. Valente, G.M. Corbo, G. Macis, A. Mule, V. Cardaci, S. Sterci, P. Granone, P. Russo, Multimodality treatment of unresectable stage III non-small cell lung cancer: Interim analysis of a phase II trial with preoperative gemcitabine and concurrent radiotherapy. J Thorac Cardiovasc Surg 131, 314–321 (2006).  https://doi.org/10.1016/j.jtcvs.2005.07.044 CrossRefPubMedGoogle Scholar
  73. 73.
    D. Planchard, S. Popat, K. Kerr, S. Novello, E.F. Smit, C. Faivre-Finn, T.S. Mok, M. Reck, P.E. Van Schil, M.D. Hellmann, S. Peters, Metastatic non-small cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 29, iv192–iv237 (2018).  https://doi.org/10.1093/annonc/mdy474 CrossRefPubMedGoogle Scholar
  74. 74.
    F. Petrella, I. Rimoldi, G. Facchetti, L. Spaggiari, Novel platinum agents and mesenchymal stromal cells for thoracic malignancies: State of the art and future perspectives. Expert Opin Ther Pat 28, 813–821 (2018).  https://doi.org/10.1080/13543776.2018.1528234 CrossRefPubMedGoogle Scholar
  75. 75.
    F. Papaccio, F. Paino, T. Regad, G. Papaccio, V. Desiderio, V. Tirino, Concise review: Cancer cells, Cancer stem cells, and Mesenchymal stem cells: Influence in Cancer development: Stem cells-Cancer stem cells interplay. Stem Cells Transl Med 6, 2115–2125 (2017).  https://doi.org/10.1002/sctm.17-0138 CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    B. Zhang, H. Shan, D. Li, Z.-R. Li, K.-S. Zhu, Z.-B. Jiang, The inhibitory effect of MSCs expressing TRAIL as a cellular delivery vehicle in combination with cisplatin on hepatocellular carcinoma. Cancer Biol Ther 13, 1175–1184 (2012).  https://doi.org/10.4161/cbt.21347 CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    M.R. Green, G.M. Manikhas, S. Orlov, B. Afanasyev, A.M. Makhson, P. Bhar, M.J. Hawkins, Abraxane®, a novel Cremophor®-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Ann Oncol 17, 1263–1268 (2006)CrossRefGoogle Scholar
  78. 78.
    J. Hu, S. Fu, Q. Peng, Y. Han, J. Xie, N. Zan, Y. Chen, J. Fan, Paclitaxel-loaded polymeric nanoparticles combined with chronomodulated chemotherapy on lung cancer: In vitro and in vivo evaluation. Int J Pharm 516, 313–322 (2017).  https://doi.org/10.1016/j.ijpharm.2016.11.047 CrossRefPubMedGoogle Scholar
  79. 79.
    T.E.G. Krueger, D.L.J. Thorek, S.R. Denmeade, J.T. Isaacs, W.N. Brennen, Concise review: Mesenchymal stem cell-based drug delivery: The good, the bad, the ugly, and the promise: MSC-based drug delivery: Good, bad, ugly, & promise. Stem Cells Transl Med 7, 651–663 (2018).  https://doi.org/10.1002/sctm.18-0024 CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    K. Antoniou, K. Karagiannis, E. Tsitoura, E. Bibaki, I. Lasithiotaki, A. Proklou, D.A. Spandidos, N. Tzanakis, Clinical applications of mesenchymal stem cells in chronic lung diseases (review). Biomed Rep (2018).  https://doi.org/10.3892/br.2018.1067

Copyright information

© International Society for Cellular Oncology 2019

Authors and Affiliations

  1. 1.Department of BiologyUniversity of HamburgHamburgGermany
  2. 2.Division of Thoracic SurgeryEuropean Institute of OncologyMilanItaly

Personalised recommendations

Cite article

Buy options