Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1997;76(7):930–934. doi: 10.1038/bjc.1997.486

Enhanced expression of vascular endothelial growth factor in metastatic melanoma.

P Salven 1, P Heikkilä 1, H Joensuu 1
PMCID: PMC2228068  PMID: 9328154

Abstract

Tumour growth is dependent on angiogenesis. Vascular endothelial growth factor (VEGF) is a secreted endothelial cell-specific cytokine. VEGF is angiogenic in vivo and it also acts as a vascular permeability factor. VEGF is overexpressed in many skin disorders characterized by angiogenesis and increased vascular permeability. We investigated VEGF expression in 22 primary cutaneous melanomas, 33 melanoma metastases and six naevocellular naevi using immunohistochemistry. VEGF accumulated on the vascular endothelia in the normal dermis, suggesting that a constitutive low level of VEGF expression may regulate skin vessel function under normal physiological conditions. No VEGF was detected in the cells of naevocellular naevi or normal dermis. In contrast, 32% of the primary and 91% of the metastatic melanomas contained melanoma cells staining for VEGF. Expression of VEGF was more frequent in metastases than in primary melanomas (P <0.0001). Tumour-infiltrating inflammatory cells expressed VEGF in all melanomas. A high number of VEGF-expressing inflammatory cells was associated with high VEGF expression in melanoma cells (P = 0.003). Our results suggest that VEGF is up-regulated during the course of melanoma progression and dissemination and that tumour-infiltrating cells expressing VEGF may contribute to the progression of melanoma.

Full text

PDF
930

Images in this article

932Figure 1
on p.932

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Banai S., Shweiki D., Pinson A., Chandra M., Lazarovici G., Keshet E. Upregulation of vascular endothelial growth factor expression induced by myocardial ischaemia: implications for coronary angiogenesis. Cardiovasc Res. 1994 Aug;28(8):1176–1179. doi: 10.1093/cvr/28.8.1176. [DOI] [PubMed] [Google Scholar]
  2. Brown L. F., Berse B., Jackman R. W., Tognazzi K., Manseau E. J., Dvorak H. F., Senger D. R. Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas. Am J Pathol. 1993 Nov;143(5):1255–1262. [PMC free article] [PubMed] [Google Scholar]
  3. Brown L. F., Harrist T. J., Yeo K. T., Ståhle-Bäckdahl M., Jackman R. W., Berse B., Tognazzi K., Dvorak H. F., Detmar M. Increased expression of vascular permeability factor (vascular endothelial growth factor) in bullous pemphigoid, dermatitis herpetiformis, and erythema multiforme. J Invest Dermatol. 1995 May;104(5):744–749. doi: 10.1111/1523-1747.ep12606974. [DOI] [PubMed] [Google Scholar]
  4. Brown L. F., Olbricht S. M., Berse B., Jackman R. W., Matsueda G., Tognazzi K. A., Manseau E. J., Dvorak H. F., Van de Water L. Overexpression of vascular permeability factor (VPF/VEGF) and its endothelial cell receptors in delayed hypersensitivity skin reactions. J Immunol. 1995 Mar 15;154(6):2801–2807. [PubMed] [Google Scholar]
  5. Brown L. F., Yeo K. T., Berse B., Yeo T. K., Senger D. R., Dvorak H. F., van de Water L. Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing. J Exp Med. 1992 Nov 1;176(5):1375–1379. doi: 10.1084/jem.176.5.1375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Carmeliet P., Ferreira V., Breier G., Pollefeyt S., Kieckens L., Gertsenstein M., Fahrig M., Vandenhoeck A., Harpal K., Eberhardt C. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature. 1996 Apr 4;380(6573):435–439. doi: 10.1038/380435a0. [DOI] [PubMed] [Google Scholar]
  7. Claffey K. P., Brown L. F., del Aguila L. F., Tognazzi K., Yeo K. T., Manseau E. J., Dvorak H. F. Expression of vascular permeability factor/vascular endothelial growth factor by melanoma cells increases tumor growth, angiogenesis, and experimental metastasis. Cancer Res. 1996 Jan 1;56(1):172–181. [PubMed] [Google Scholar]
  8. Denijn M., Ruiter D. J. The possible role of angiogenesis in the metastatic potential of human melanoma. Clinicopathological aspects. Melanoma Res. 1993 Feb;3(1):5–14. doi: 10.1097/00008390-199304000-00002. [DOI] [PubMed] [Google Scholar]
  9. Detmar M., Brown L. F., Claffey K. P., Yeo K. T., Kocher O., Jackman R. W., Berse B., Dvorak H. F. Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis. J Exp Med. 1994 Sep 1;180(3):1141–1146. doi: 10.1084/jem.180.3.1141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dvorak H. F., Brown L. F., Detmar M., Dvorak A. M. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995 May;146(5):1029–1039. [PMC free article] [PubMed] [Google Scholar]
  11. Dvorak H. F., Sioussat T. M., Brown L. F., Berse B., Nagy J. A., Sotrel A., Manseau E. J., Van de Water L., Senger D. R. Distribution of vascular permeability factor (vascular endothelial growth factor) in tumors: concentration in tumor blood vessels. J Exp Med. 1991 Nov 1;174(5):1275–1278. doi: 10.1084/jem.174.5.1275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ferrara N., Carver-Moore K., Chen H., Dowd M., Lu L., O'Shea K. S., Powell-Braxton L., Hillan K. J., Moore M. W. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature. 1996 Apr 4;380(6573):439–442. doi: 10.1038/380439a0. [DOI] [PubMed] [Google Scholar]
  13. Ferrara N. The role of vascular endothelial growth factor in pathological angiogenesis. Breast Cancer Res Treat. 1995;36(2):127–137. doi: 10.1007/BF00666035. [DOI] [PubMed] [Google Scholar]
  14. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995 Jan;1(1):27–31. doi: 10.1038/nm0195-27. [DOI] [PubMed] [Google Scholar]
  15. Freeman M. R., Schneck F. X., Gagnon M. L., Corless C., Soker S., Niknejad K., Peoples G. E., Klagsbrun M. Peripheral blood T lymphocytes and lymphocytes infiltrating human cancers express vascular endothelial growth factor: a potential role for T cells in angiogenesis. Cancer Res. 1995 Sep 15;55(18):4140–4145. [PubMed] [Google Scholar]
  16. Gasparini G., Harris A. L. Clinical importance of the determination of tumor angiogenesis in breast carcinoma: much more than a new prognostic tool. J Clin Oncol. 1995 Mar;13(3):765–782. doi: 10.1200/JCO.1995.13.3.765. [DOI] [PubMed] [Google Scholar]
  17. Gutman M., Singh R. K., Yoon S., Xie K., Bucana C. D., Fidler I. J. Leukocyte-induced angiogenesis and subcutaneous growth of B16 melanoma. Cancer Biother. 1994 Summer;9(2):163–170. doi: 10.1089/cbr.1994.9.163. [DOI] [PubMed] [Google Scholar]
  18. Hanahan D., Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996 Aug 9;86(3):353–364. doi: 10.1016/s0092-8674(00)80108-7. [DOI] [PubMed] [Google Scholar]
  19. Hatva E., Kaipainen A., Mentula P., Jäskeläinen J., Paetau A., Haltia M., Alitalo K. Expression of endothelial cell-specific receptor tyrosine kinases and growth factors in human brain tumors. Am J Pathol. 1995 Feb;146(2):368–378. [PMC free article] [PubMed] [Google Scholar]
  20. Pötgens A. J., Lubsen N. H., van Altena M. C., Schoenmakers J. G., Ruiter D. J., de Waal R. M. Vascular permeability factor expression influences tumor angiogenesis in human melanoma lines xenografted to nude mice. Am J Pathol. 1995 Jan;146(1):197–209. [PMC free article] [PubMed] [Google Scholar]
  21. Shweiki D., Itin A., Soffer D., Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature. 1992 Oct 29;359(6398):843–845. doi: 10.1038/359843a0. [DOI] [PubMed] [Google Scholar]
  22. Shweiki D., Neeman M., Itin A., Keshet E. Induction of vascular endothelial growth factor expression by hypoxia and by glucose deficiency in multicell spheroids: implications for tumor angiogenesis. Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):768–772. doi: 10.1073/pnas.92.3.768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Weidner N., Semple J. P., Welch W. R., Folkman J. Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. N Engl J Med. 1991 Jan 3;324(1):1–8. doi: 10.1056/NEJM199101033240101. [DOI] [PubMed] [Google Scholar]
  24. Weninger W., Uthman A., Pammer J., Pichler A., Ballaun C., Lang I. M., Plettenberg A., Bankl H. C., Stürzl M., Tschachler E. Vascular endothelial growth factor production in normal epidermis and in benign and malignant epithelial skin tumors. Lab Invest. 1996 Nov;75(5):647–657. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES