Distinct CXC chemokines mediate tumorigenicity of prostate cancer cells

Am J Pathol. 1999 May;154(5):1503-12. doi: 10.1016/S0002-9440(10)65404-1.


Prostate cancer is the second leading cause of malignancy-related mortality in males in the United States. As a solid tumor, clinically significant tumor growth and metastasis are dependent on nutrients and oxygen supplied by tumor-associated neovasculature. As such, there is a selective tumorigenic advantage for those neoplasms that can produce angiogenic mediators. We show here that human prostate cancer cell lines can constitutively produce angiogenic CXC chemokines. Tumorigenesis of PC-3 prostate cancer cells was shown to be attributable, in part, to the production of the angiogenic CXC chemokine, interleukin (IL)-8. Neutralizing antisera to IL-8 inhibits PC-3 tumor growth in a human prostate cancer/SCID mouse model. Furthermore, angiogenic activity in PC-3 tumor homogenates was attributable to IL-8. In contrast, the Du145 prostate cancer cell line uses a different angiogenic CXC chemokine, GRO-alpha, to mediate tumorigenicity. Neutralizing antisera to GRO-alpha but not IL-8 reduced tumor growth in vivo and reduced the angiogenic activity in tumor homogenates. Thus, prostate cancer cell lines can use distinct CXC chemokines to mediate their tumorigenicity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chemokines, CXC / physiology*
  • Humans
  • Male
  • Mice
  • Mice, SCID
  • Neovascularization, Pathologic
  • Paracrine Communication / physiology
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / physiopathology*
  • Severe Combined Immunodeficiency / pathology
  • Severe Combined Immunodeficiency / physiopathology
  • Tumor Cells, Cultured


  • Chemokines, CXC