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Am J Pathol. 1999 May;154(5):1503-12.

Distinct CXC chemokines mediate tumorigenicity of prostate cancer cells.

Author information

1
Departments of Internal Medicine and Pathology and the Undergraduate Research Opportunities Program, University of Michigan Medical Center, Ann Arbor, Michigan, USA.

Abstract

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.

PMID:
10329603
PMCID:
PMC1866583
DOI:
10.1016/S0002-9440(10)65404-1
[Indexed for MEDLINE]
Free PMC Article

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