Display options
Cite
Zhou L, Yang K, Andl T, et al. Perspective of Targeting Cancer-Associated Fibroblasts in Melanoma. J Cancer. 2015;6(8):717-26doi: 10.7150/jca.10865.
Zhou, L., Yang, K., Andl, T., Wickett, R. R., & Zhang, Y. (2015). Perspective of Targeting Cancer-Associated Fibroblasts in Melanoma. Journal of Cancer, 6(8), 717-26. https://doi.org/10.7150/jca.10865
Zhou, Linli, et al. "Perspective of Targeting Cancer-Associated Fibroblasts in Melanoma." Journal of Cancer vol. 6,8 (2015): 717-26. doi: https://doi.org/10.7150/jca.10865
Zhou L, Yang K, Andl T, Wickett RR, Zhang Y. Perspective of Targeting Cancer-Associated Fibroblasts in Melanoma. J Cancer. 2015 Jun 23;6(8):717-26. doi: 10.7150/jca.10865. eCollection 2015. PMID: 26185533; PMCID: PMC4504107.
Copy Download .nbib Format: NLM
Share it on

J Cancer. 2015 Jun 23;6(8):717-26. doi: 10.7150/jca.10865. eCollection 2015.

Perspective of Targeting Cancer-Associated Fibroblasts in Melanoma.

Journal of Cancer

Linli Zhou, Kun Yang, Thomas Andl, R Randall Wickett, Yuhang Zhang

Affiliations

  1. 1. Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267, USA.
  2. 2. Division of Dermatology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2600, USA.

PMID: 26185533 PMCID: PMC4504107 DOI: 10.7150/jca.10865

Abstract

Melanoma is known as an exceptionally aggressive and treatment-resistant human cancer. Although a great deal of progress has been made in the past decade, including the development of immunotherapy using immune checkpoint inhibitors and targeted therapy using BRAF, MEK or KIT inhibitors, treatment for unresectable stage III, stage IV, and recurrent melanoma is still challenging with limited response rate, severe side effects and poor prognosis, highlighting an urgent need for discovering and designing more effective approaches to conquer melanoma. Melanoma is not only driven by malignant melanocytes, but also by the altered communication between neoplastic cells and non-malignant cell populations, including fibroblasts, endothelial and inflammatory cells, in the tumor stroma. Infiltrated and surrounding fibroblasts, also known as cancer-associated fibroblasts (CAFs), exhibit both phenotypical and physiological differences compared to normal dermal fibroblasts. They acquire properties of myofibroblasts, remodel the extracellular matrix (ECM) and architecture of the diseased tissue and secrete chemical factors, which all together promote the transformation process by encouraging tumor growth, angiogenesis, inflammation and metastasis and contribute to drug resistance. A number of in vitro and in vivo experiments have shown that stromal fibroblasts promote melanoma cell proliferation and they have been targeted to suppress tumor growth effectively. Evidently, a combination therapy co-targeting tumor cells and stromal fibroblasts may provide promising strategies to improve therapeutic outcomes and overcome treatment resistance. A significant benefit of targeting CAFs is that the approach aims to create a tumor-resistant environment that inhibits growth of melanomas carrying different genetic mutations. However, the origin of CAFs and precise mechanisms by which CAFs contribute to melanoma progression and drug resistance remain poorly understood. In this review, we discuss the origin, activation and heterogeneity of CAFs in the melanoma tumor microenvironment and examine the contributions of stromal fibroblasts at different stages of melanoma development. We also highlight the recent progression in dissecting and characterizing how local fibroblasts become reprogrammed and build a dynamic yet optimal microenvironment for tumors to develop and metastasize. In addition, we review key developments in ongoing preclinical studies and clinical applications targeting CAFs and tumor-stroma interactions for melanoma treatment.

Keywords: cancer-associated fibroblasts; melanoma; skin cancer; tumor microenvironment

References

  1. Eur J Cancer. 1999 Mar;35(3):473-80 - PubMed
  2. Am J Cancer Res. 2011;1(4):482-97 - PubMed
  3. Cancer Metastasis Rev. 2001;20(1-2):3-11 - PubMed
  4. Nat Rev Cancer. 2004 Jul;4(7):528-39 - PubMed
  5. Mol Cancer Res. 2009 Aug;7(8):1212-23 - PubMed
  6. J Biol Chem. 2014 Mar 21;289(12 ):8442-9 - PubMed
  7. J Skin Cancer. 2013;2013:423829 - PubMed
  8. PLoS One. 2013;8(4):e60321 - PubMed
  9. Curr Probl Cancer. 2011 Jul-Aug;35(4):173-84 - PubMed
  10. Cancer Res. 2013 Sep 1;73(17 ):5347-59 - PubMed
  11. Oncologist. 2011;16(1):5-24 - PubMed
  12. Cancer Immunol Immunother. 2012 Feb;61(2):145-55 - PubMed
  13. Cancer Res. 1999 Oct 1;59(19):5002-11 - PubMed
  14. Cancer Res. 2005 Dec 1;65(23):11156-63 - PubMed
  15. Br J Dermatol. 2012 Jun;166(6):1184-97 - PubMed
  16. Eur J Cancer. 2001 Nov;37(17):2147-53 - PubMed
  17. J Biol Chem. 2001 Jul 6;276(27):24661-6 - PubMed
  18. Mol Cancer. 2010 Jul 28;9:201 - PubMed
  19. Lancet Oncol. 2006 Feb;7(2):167-74 - PubMed
  20. Semin Cell Dev Biol. 2010 Feb;21(1):2-10 - PubMed
  21. Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3414-9 - PubMed
  22. J Clin Invest. 2009 Dec;119(12):3613-25 - PubMed
  23. Br J Cancer. 2013 Apr 30;108(8):1634-40 - PubMed
  24. Pigment Cell Melanoma Res. 2009 Apr;22(2):175-86 - PubMed
  25. Histol Histopathol. 2009 May;24(5):643-50 - PubMed
  26. Anticancer Res. 2013 Sep;33(9):3715-23 - PubMed
  27. J Cell Biochem. 2007 Jul 1;101(4):805-15 - PubMed
  28. J Cell Biol. 2012 Feb 20;196(4):395-406 - PubMed
  29. J Invest Dermatol. 2005 Mar;124(3):638-43 - PubMed
  30. Annu Rev Med. 2002;53:615-27 - PubMed
  31. Pathol Biol (Paris). 2005 Sep;53(7):372-82 - PubMed
  32. Oncologist. 2013 Jun;18(6):717-25 - PubMed
  33. J Signal Transduct. 2012;2012:684592 - PubMed
  34. PLoS One. 2012;7(6):e38811 - PubMed
  35. J Cell Sci. 1994 Apr;107 ( Pt 4):983-92 - PubMed
  36. Cancer Lett. 2012 Nov 1;324(1):31-41 - PubMed
  37. Cancer Res. 2003 Oct 15;63(20):6751-7 - PubMed
  38. Med Sci (Paris). 2014 Apr;30(4):391-7 - PubMed
  39. Clin Dermatol. 2013 May-Jun;31(3):282-9 - PubMed
  40. Arch Dermatol Res. 2003 Nov;295(6):236-41 - PubMed
  41. Int J Oncol. 2011 Jul;39(1):193-202 - PubMed
  42. Nat Rev Cancer. 2006 May;6(5):392-401 - PubMed
  43. Expert Opin Ther Targets. 2005 Dec;9(6):1217-33 - PubMed
  44. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9215-9 - PubMed
  45. Oncogene. 2011 Oct 20;30(42):4316-26 - PubMed
  46. J Drugs Dermatol. 2014 May;13(5):586-8 - PubMed
  47. Br J Dermatol. 2013 Sep;169(3):618-28 - PubMed
  48. J Clin Oncol. 2006 Sep 10;24(26):4340-6 - PubMed
  49. Am J Pathol. 2000 Sep;157(3):957-65 - PubMed
  50. Am J Pathol. 2000 May;156(5):1515-25 - PubMed
  51. Cancer Res. 2002 Dec 15;62(24):7328-34 - PubMed
  52. Breast Cancer Res Treat. 2008 Jul;110(1):39-49 - PubMed
  53. Int J Mol Sci. 2012;13(8):9545-71 - PubMed
  54. Cancer Res. 2001 Nov 15;61(22):8306-16 - PubMed
  55. Cell Cycle. 2005 Oct;4(10):1382-4 - PubMed
  56. Cancer Res. 2005 May 15;65(10):4134-46 - PubMed
  57. Cancer Res. 2001 May 1;61(9):3819-25 - PubMed
  58. Ann Oncol. 2013 Jun;24(6):1691-7 - PubMed
  59. Nature. 2013 Feb 14;494(7436):251-5 - PubMed
  60. J Biol Chem. 2003 Jul 11;278(28):25285-8 - PubMed
  61. Clin Cancer Res. 2012 Mar 1;18(5):1457-63 - PubMed
  62. Nature. 2012 Jul 26;487(7408):500-4 - PubMed
  63. PLoS Med. 2008 Jan 29;5(1):e19 - PubMed
  64. Cell Cycle. 2009 May 15;8(10):1461-2 - PubMed
  65. J Clin Oncol. 2014 Apr 1;32(10):986-8 - PubMed
  66. Pigment Cell Melanoma Res. 2014 Nov;27(6):1154-8 - PubMed
  67. Exp Cell Res. 2010 Oct 15;316(17):2713-22 - PubMed
  68. Cancer Biol Ther. 2012 Feb 1;13(3):123-9 - PubMed
  69. Adv Pharmacol. 2012;65:335-59 - PubMed
  70. Semin Cell Dev Biol. 2010 Feb;21(1):19-25 - PubMed
  71. J Invest Dermatol. 2003 Feb;120(2):182-8 - PubMed
  72. Cancers (Basel). 2013 Jan 31;5(1):149-69 - PubMed
  73. Curr Pharm Biotechnol. 2011 Dec;12(12):2165-75 - PubMed
  74. Neoplasia. 2009 Dec;11(12):1264-71 - PubMed
  75. Curr Opin Oncol. 2010 May;22(3):178-83 - PubMed
  76. Stem Cells. 2014 Jan;32(1):145-56 - PubMed
  77. Int J Cancer. 2009 Oct 15;125(8):1796-804 - PubMed
  78. Nat Med. 2011 Mar;17(3):320-9 - PubMed
  79. Oncogene. 2005 Feb 17;24(8):1423-33 - PubMed
  80. Int J Cancer. 2012 Nov 15;131(10):2274-83 - PubMed
  81. Oncogene. 2005 Jul 28;24(32):5053-68 - PubMed
  82. J Biol Chem. 2005 May 27;280(21):20310-5 - PubMed
  83. Oncogene. 2004 May 20;23(23):4060-7 - PubMed
  84. Sci Transl Med. 2014 May 28;6(238):238ra70 - PubMed
  85. Scientifica (Cairo). 2013;2013:635203 - PubMed
  86. J Natl Cancer Inst. 2007 Oct 3;99(19):1441-54 - PubMed
  87. Melanoma Res. 2013 Dec;23 (6):434-43 - PubMed
  88. J Biol Chem. 2011 Feb 25;286(8):6801-7 - PubMed
  89. J Clin Invest. 2006 Jul;116(7):1955-62 - PubMed
  90. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6028-32 - PubMed
  91. Br J Cancer. 2002 Jan 21;86(2):179-84 - PubMed
  92. Cancer Cell. 2009 Jan 6;15(1):3-5 - PubMed
  93. Mol Pharm. 2011 Dec 5;8(6):2039-49 - PubMed
  94. Front Oncol. 2014 Mar 27;4:62 - PubMed
  95. Ann Oncol. 2012 Oct;23 Suppl 7:vii86-91 - PubMed
  96. J Dermatolog Treat. 2014 Oct;25(5):401-8 - PubMed
  97. J Biol Chem. 2012 Aug 10;287(33):28087-98 - PubMed
  98. Mol Cancer Ther. 2012 Nov;11(11):2516-25 - PubMed
  99. Cancer Discov. 2014 Jan;4(1):80-93 - PubMed
  100. Int J Cancer. 2001 Sep 1;93(5):617-22 - PubMed
  101. EXS. 1993;65:329-39 - PubMed
  102. Curr Oncol Rep. 2008 Sep;10(5):439-46 - PubMed
  103. J Cutan Pathol. 2012 Sep;39(9):826-34 - PubMed
  104. Tissue Eng Part A. 2014 Sep;20(17-18):2412-21 - PubMed
  105. Int J Oncol. 1994 Nov;5(5):1125-30 - PubMed
  106. Mol Cancer Res. 2014 May;12(5):795-802 - PubMed
  107. Br J Cancer. 2014 Jan 21;110(2):469-78 - PubMed
  108. Cancer Sci. 2008 Sep;99(9):1720-5 - PubMed
  109. Front Biosci (Landmark Ed). 2010 Jan 01;15:166-79 - PubMed
  110. Carcinogenesis. 2009 Jan;30(1):20-7 - PubMed
  111. Cancer. 2014 May 1;120(9):1361-8 - PubMed
  112. Clin Cancer Res. 2005 Mar 1;11(5):1835-41 - PubMed
  113. Pigment Cell Melanoma Res. 2011 Apr;24(2):382-5 - PubMed
  114. Pharmacol Ther. 2014 May;142(2):176-82 - PubMed
  115. J Leukoc Biol. 2011 Jan;89(1):31-9 - PubMed
  116. Cancer Biol Ther. 2008 Aug;7(8):1212-25 - PubMed
  117. Cancer Treat Rev. 2013 Dec;39(8):879-85 - PubMed
  118. Cancer Res. 2008 Feb 1;68(3):918-26 - PubMed
  119. J Invest Dermatol. 2010 Jan;130(1):20-7 - PubMed
  120. Exp Dermatol. 2000 Feb;9(1):34-41 - PubMed
  121. Arzneimittelforschung. 2008;58(6):261-4 - PubMed
  122. Cancer. 2008 Mar 1;112(5):982-94 - PubMed
  123. Cell. 2005 May 6;121(3):335-48 - PubMed
  124. Am J Ther. 2015 Jan-Feb;22(1):44-53 - PubMed
  125. J Natl Cancer Inst. 2003 Dec 17;95(24):1878-90 - PubMed
  126. Br J Cancer. 2008 Dec 16;99(12):2065-9 - PubMed

Publication Types