Expression of lnterleukin-8 Correlates with Angiogenesis, Tumorigenicity, and Metastasis of Human Prostate Cancer Cells Implanted Orthotopically in Nude Mice1
| Autor: | Sun, Jin Kim, Uehara, Hisanori, Karashima, Takashi, Mccarty, Marya, Shih, Nancy, Fidler, Isaiah J |
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| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Lymphokines Mice Inbred BALB C Neovascularization Pathologic Vascular Endothelial Growth Factors Interleukin-8 Mice Nude Prostatic Neoplasms Endothelial Growth Factors Blotting Northern Cadherins Mice Lymphatic Metastasis Tumor Cells Cultured Animals Humans Matrix Metalloproteinase 2 Fibroblast Growth Factor 2 Neoplasm Invasiveness RNA Messenger In Situ Hybridization Neoplasm Transplantation Research Article DNA Primers |
| Popis: | We determined whether the expression of interleukin-8 (IL-8) by human prostate cancer cells correlates with induction of angiogenesis, tumorigenicity, and production of metastasis. Low and high IL-8-producing clones were isolated from the heterogeneous PC-3 human prostate cancer cell line. The secretion of IL-8 protein correlated with transcriptional activity and levels of IL-8 mRNA. All PC-3 cells expressed both IL-8 receptors, CXCR1 and CXCR2. The low and high IL-8-producing clones were injected into the prostate of nude mice. Titration studies indicated that PC-3 cells expressing high levels of IL-8 were highly tumorigenic, producing rapidly growing, highly vascularized prostate tumors with and a 100% incidence of lymph node metastasis. Low IL-8-expressing PC-3 cells were less tumorigenic, producing slower growing and less vascularized primary tumors and a significantly lower incidence of metastasis. In situ hybridization (ISH) analysis of the tumors for expression of genes that regulate angiogenesis and metastasis showed that the expression level of IL-8, matrix metalloproteinases, vascular endothelial growth factor (VEGF), and E-cadherin corresponded with microvascular density and biological behavior of the prostate cancers in nude mice. Collectively, the data show that the expression level of IL-8 in human prostate cancer cells is associated with angiogenesis, tumorigenicity, and metastasis. |
| Databáze: | OpenAIRE |
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