ABSTRACT
Although prostate cancer is still the most diagnosed cancer in men, most genes implicated in its progression are yet to be identified. Chromosome abnormalities have been detected in human prostate tumors, many of them associated with prostate cancer progression. Indeed, alterations (including deletions or amplifications) of more than 15 human chromosomes have been reported in prostate cancer. We hypothesized that transferring normal human chromosomes into human prostate cancer cells would interfere with their tumorigenic and/or metastatic properties. We used microcell-mediated chromosome transfer to introduce human chromosomes 10, 12, 17, and 18 into highly tumorigenic (PC-3M-Pro4) and highly metastatic (PC-3M-LN4) PC-3-derived cell lines. We tested the in vitro and in vivo properties of these hybrids. Introducing chromosome 18 into the PC-3M-LN4 prostate cancer cell line greatly reduced its tumorigenic phenotype. We observed retarded growth in soft agar, decreased invasiveness through Matrigel, and delayed tumor growth into nude mice, both subcutaneously and orthotopically. This phenotype is associated with a marker in the 18q21 region. Combined with the loss of human chromosome 18 regions often seen in patients with advanced prostate cancer, our results show that chromosome 18 encodes one or more tumor-suppressor genes whose inactivation contributes to prostate cancer progression.
Subject(s)
Chromosomes, Human/physiology , Prostatic Neoplasms/pathology , Animals , Cell Line, Tumor , Chromosomes, Human, Pair 18/physiology , Humans , Hybrid Cells/pathology , Male , Mice , Mice, Nude , Neoplasm Invasiveness , Neoplasm Transplantation , Transplantation, Heterologous/pathologyABSTRACT
Expression of tetraspanin CD9 protein is downregulated in many tumors. CD9 over-expression also reduces the tumorigenicity of some human cancer cells. Here, we determined if exogenous expression of CD9 affects the properties of human prostate cancer cells. Highly metastatic prostate cancer cells PC-3M-LN4 over-expressing exogenous CD9 were orthotopically injected into the prostate of nude mice. CD9 expression was determined in tumors using PCR and Western immunoblotting techniques. Over-expression of CD9 increased invasiveness of prostate cancer cells in vitro. Animals injected with either parental PC-3M-LN4 or CD9-transfected cells developed tumor and harbored lymph node metastasis. There was no statistical difference in tumor growth between the two cell lines. CD9 did not suppress tumorigenic or metastatic properties of PC-3M-LN4 cells. Our data contrast with published results in other tumor types and likely indicate that other proteins (CD9 partners) are needed for CD9 full anti-tumorigenic action.
