The Role of Caveolin-1 in Skin Cancer

  • Alessandra Carè
  • Isabella Parolini
  • Federica Felicetti
  • Massimo Sargiacomo
Part of the Current Cancer Research book series (CUCR)


Caveolin-1 (Cav-1) expression in human cancer has extensively been documented in cell lines and primary tumors. Type and stage of tumor often modulates Cav-1 levels, which results in either down or upregulation depending on cancer types. Among all skin cancers, melanoma is by far the most regulated by Cav-1. The role of Cav-1 in tumor progression of primary and metastatic melanoma appears discordant since it can stimulate or inhibit tumor growth. Studies on Cav-1 signaling in different tumor types can reveal exploitable analogies useful to better interpret the behavior of Cav-1 in melanoma. We have originally characterized Cav-1-containing exosomes in human melanoma cell lines, described their fusion ability with target cells, and their adaptability to low micro enviromental pH. These nano scale cell-secreted vesicles contain Cav-1 and a number of melanoma progression markers, which can also be traced into the plasma of poor prognosis patients affected by melanoma.


Melanoma Cell Melanoma Cell Line Human Melanoma Cell B16F10 Cell Melanoma Tissue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank G. Loreto for preparation of the figures. This work was partially supported by the Italian Ministry of Health (to MS and AC) and by the Italian Association for Cancer Research to AC.


  1. 1.
    Al-Nedawi K, Meehan B, Micallef J et al (2008) Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol 10:619–624PubMedCrossRefGoogle Scholar
  2. 2.
    Al-Nedawi K, Meehan B, Rak J (2009) Microvesicles: Messengers and mediators of tumor progression. Cell Cycle 8:2014–2018PubMedCrossRefGoogle Scholar
  3. 3.
    Burgermeister E, Liscovitch M, Rocken C et al (2008) Caveats of caveolin-1 in cancer progression. Cancer Lett 268:187–201PubMedCrossRefGoogle Scholar
  4. 4.
    Burgermeister E, Xing X, Rocken C et al (2007) Differential expression and function of caveolin-1 in human gastric cancer progression. Cancer Res 67:8519–8526PubMedCrossRefGoogle Scholar
  5. 5.
    De Milito A, Iessi E, Logozzi M et al (2007) Proton pump inhibitors induce apoptosis of human B-cell tumors through a caspase-independent mechanism involving reactive oxygen species. Cancer Res 67:5408–5417PubMedCrossRefGoogle Scholar
  6. 6.
    del Pozo MA, Balasubramanian N, Alderson NB et al (2005) Phospho-caveolin-1 mediates integrin-regulated membrane domain internalization. Nat Cell Biol 7:901–908PubMedCrossRefGoogle Scholar
  7. 7.
    Di Vizio D, Morello M, Sotgia F et al (2009) An absence of stromal caveolin-1 is associated with advanced prostate cancer, metastatic disease and epithelial akt activation. Cell Cycle 8:2420–2424PubMedCrossRefGoogle Scholar
  8. 8.
    Felicetti F, Errico MC, Bottero L et al (2008) The promyelocytic leukemia zinc finger-microRNA-221/-222 pathway controls melanoma progression through multiple oncogenic mechanisms. Cancer Res 68:2745–2754PubMedCrossRefGoogle Scholar
  9. 9.
    Felicetti F, Parolini I, Bottero L et al (2009) Caveolin-1 tumor-promoting role in human melanoma. Int J Cancer 125:1514–1522PubMedCrossRefGoogle Scholar
  10. 10.
    Hood JL, Pan H, Lanza GM et al (2009) Paracrine induction of endothelium by tumor exosomes. Lab Invest 89:1317–1328PubMedCrossRefGoogle Scholar
  11. 11.
    Joo HJ, Oh DK, Kim YS et al (2004) Increased expression of caveolin-1 and microvessel density correlates with metastasis and poor prognosis in clear cell renal cell carcinoma. BJU Int 93:291–296PubMedCrossRefGoogle Scholar
  12. 12.
    Karam JA, Lotan Y, Roehrborn G et al (2007) Caveolin-1 overexpression is associated with aggressive prostate cancer recurrence. Prostate 67:614–622PubMedCrossRefGoogle Scholar
  13. 13.
    Kaucic K, Liu Y, Ladisch S (2006) Modulation of growth factor signaling by gangliosides: Positive or negative? Methods Enzymol 417:168–185PubMedCrossRefGoogle Scholar
  14. 14.
    Kosaka N, Iguchi H, Ochiya T (2010) Circulating microRNA in body fluid: A new potential biomarker for cancer diagnosis and prognosis. Cancer Sci 101:2087–2092PubMedCrossRefGoogle Scholar
  15. 15.
    Llorente A, de Marco MC, Alonso MA (2004) Caveolin-1 and MAL are located on prostasomes secreted by the prostate cancer PC-3 cell line. J Cell Sci 117:5343–5351PubMedCrossRefGoogle Scholar
  16. 16.
    Logozzi M, De Milito A, Lugini L et al (2009) High levels of exosomes expressing CD63 and caveolin-1 in plasma of melanoma patients. PLoS One 4:e5219PubMedCrossRefGoogle Scholar
  17. 17.
    Lugini L, Matarrese P, Tinari A et al (2006) Cannibalism of live lymphocytes by human metastatic but not primary melanoma cells. Cancer Res 66:3629–3638PubMedCrossRefGoogle Scholar
  18. 18.
    Miller AJ, Mihm MC Jr (2006) Melanoma. N Engl J Med 355:51–65PubMedCrossRefGoogle Scholar
  19. 19.
    Miyanishi M, Tada K, Koike M et al (2007) Identification of Tim4 as a phosphatidylserine receptor. Nature 450:435–439PubMedCrossRefGoogle Scholar
  20. 20.
    Morelli AE, Larregina AT, Shufesky WJ et al (2004) Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. Blood 104:3257–3266PubMedCrossRefGoogle Scholar
  21. 21.
    Nicolson GL, Brunson KW, Fidler IJ (1978) Specificity of arrest, survival, and growth of selected metastatic variant cell lines. Cancer Res 38:4105–4111PubMedGoogle Scholar
  22. 22.
    Parolini I, Federici C, Raggi C et al (2009) Microenvironmental pH is a key factor for exosome traffic in tumor cells. J Biol Chem 284:34211–34222PubMedCrossRefGoogle Scholar
  23. 23.
    Sargiacomo M, Scherer PE, Tang Z et al (1995) Oligomeric structure of caveolin: Implications for caveolae membrane organization. Proc Natl Acad Sci USA 92:9407–9411PubMedCrossRefGoogle Scholar
  24. 24.
    Satoh T, Yang G, Egawa S et al (2003) Caveolin-1 expression is a predictor of recurrence-free survival in pT2N0 prostate carcinoma diagnosed in japanese patients. Cancer 97:1225–1233PubMedCrossRefGoogle Scholar
  25. 25.
    Savage K, Lambros MB, Robertson D et al (2007) Caveolin 1 is overexpressed and amplified in a subset of basal-like and metaplastic breast carcinomas: A morphologic, ultrastructural, immunohistochemical, and in situ hybridization analysis. Clin Cancer Res 13:90–101PubMedCrossRefGoogle Scholar
  26. 26.
    Segura E, Guerin C, Hogg N et al (2007) CD8+ dendritic cells use LFA-1 to capture MHC-peptide complexes from exosomes in vivo. J Immunol 179:1489–1496PubMedGoogle Scholar
  27. 27.
    Shatz M, Liscovitch M (2008) Caveolin-1: A tumor-promoting role in human cancer. Int J Radiat Biol 84:177–189PubMedCrossRefGoogle Scholar
  28. 28.
    Tahir SA, Frolov A, Hayes TG et al (2006) Preoperative serum caveolin-1 as a prognostic marker for recurrence in a radical prostatectomy cohort. Clin Cancer Res 12:4872–4875PubMedCrossRefGoogle Scholar
  29. 29.
    Thery C, Ostrowski M, Segura E (2009) Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 9:581–593PubMedCrossRefGoogle Scholar
  30. 30.
    Thompson TC, Tahir SA, Li L et al (2010) The role of caveolin-1 in prostate cancer: Clinical implications. Prostate Cancer Prostatic Dis 13:6–11PubMedCrossRefGoogle Scholar
  31. 31.
    Trimmer C, Whitaker-Menezes D, Bonuccelli G et al (2010) CAV1 inhibits metastatic potential in melanomas through suppression of the integrin/Src/FAK signaling pathway. Cancer Res 70:7489–7499PubMedCrossRefGoogle Scholar
  32. 32.
    Valadi H, Ekstrom K, Bossios A et al (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9:654–659PubMedCrossRefGoogle Scholar
  33. 33.
    Wary KK, Mariotti A, Zurzolo C , Giancotti FG (1998) A requirement for Caveolin-1 and associated kinase Fyn in integrin signalling and anchorage –dependent cell growth. Cell 94:625–634PubMedCrossRefGoogle Scholar
  34. 34.
    Williams TM, Lisanti MP (2005) Caveolin-1 in oncogenic transformation, cancer, and metastasis. Am J Physiol Cell Physiol 288:C494–C506PubMedCrossRefGoogle Scholar
  35. 35.
    Yamamura S, Handa K, Hakomori S (1997) A close association of GM3 with c-src and rho in GM3-enriched microdomains at the B16 melanoma cell surface membrane: A preliminary note. Biochem Biophys Res Commun 236:218–222PubMedCrossRefGoogle Scholar
  36. 36.
    Yang G, Addai J, Wheeler TM et al (2007) Correlative evidence that prostate cancer cell-derived caveolin-1 mediates angiogenesis. Hum Pathol 38:1688–1695PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Alessandra Carè
    • 1
  • Isabella Parolini
    • 1
  • Federica Felicetti
    • 1
  • Massimo Sargiacomo
    • 1
  1. 1.Department of Hematology, Oncology and Molecular MedicineIstituto Superiore di SanitàRomeItaly

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