Int J Biol Sci 2008; 4(4):246-258. doi:10.7150/ijbs.4.246
Bad seeds produce bad crops: a single stage-process of prostate tumor invasion
1. American Registry of Pathology and Armed Forces Institute of Pathology, Washington DC, USA
2. Jilin University, Changchun, Jilin, China
Man Yg, Gardner WA. Bad seeds produce bad crops: a single stage-process of prostate tumor invasion. Int J Biol Sci 2008; 4(4):246-258. doi:10.7150/ijbs.4.246. Available from http://www.ijbs.com/v04p0246.htm
It is a commonly held belief that prostate carcinogenesis is a multi-stage process and that tumor invasion is triggered by the overproduction of proteolytic enzymes. This belief is consistent with data from cell cultures and animal models, whereas is hard to interpret several critical facts, including the presence of cancer in “healthy” young men and cancer DNA phenotype in morphologically normal prostate tissues. These facts argue that alternative pathways may exist for prostate tumor invasion in some cases. Since degradation of the basal cell layer is the most distinct sign of invasion, our recent studies have attempted to identify pre-invasive lesions with focal basal cell layer alterations. Our studies revealed that about 30% of prostate cancer patients harbored normal appearing duct or acinar clusters with a high frequency of focal basal cell layer disruptions. These focally disrupted basal cell layers had significantly reduced cell proliferation and tumor suppressor expression, whereas significantly elevated degeneration, apoptosis, and infiltration of immunoreactive cells. In sharp contrast, associated epithelial cell had significantly elevated proliferation, expression of malignancy-signature markers, and physical continuity with invasive lesions. Based on these and other findings, we have proposed that these normal appearing duct or acinar clusters are derived from monoclonal proliferation of genetically damaged stem cells and could progress directly to invasion through two pathways: 1) clonal in situ transformation (CIST) and 2) multi-potential progenitor mediated “budding” (MPMB). These pathways may contribute to early onset of prostate cancer at young ages, and to clinically more aggressive prostate tumors.
Keywords: prostate carcinogenesis, tumor invasion, pre-invasive lesions