Expression of interleukin-8 correlates with angiogenesis, tumorigenicity, and metastasis of human prostate cancer cells implanted orthotopically in nude mice.
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.
Kim
S J
SJ
Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Uehara
H
H
Karashima
T
T
Mccarty
M
M
Shih
N
N
Fidler
I J
IJ
D000818:Animals; D015152:Blotting, Northern; D015820:Cadherins / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D016228:Endothelial Growth Factors / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D016209:Interleukin-8 / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D015820:Cadherins; D017931:DNA Primers; D016228:Endothelial Growth Factors; D016209:Interleukin-8; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D020778:Matrix Metalloproteinase 2