Heterogeneous Expression of Invasive and Metastatic Properties in a Prostate Tumor Model

Cellular heterogeneity of neoplasia is well demonstrated in the Dunning R-3327 rat prostate adenocarcinoma. In this study, we measured the differential expression of invasive and metastatic properties of this prostate model by cloning from a heterogeneous parental cell line. Four cell clones were derived and characterized by morphological studies, E-cadherin expression, and invasive and metastatic potential. Three of the clones (clones 5A, 5C, and 5D) demonstrated a fibroblastic morphology and were anchored to the substrate by loose microvillous processes. The fourth clone (clone 5B) grew in tight clusters and displayed many closely spaced microvilli, long overlapping cytoplasmic regions with well-defined junctional complexes. The parental line (R3327-5) demonstrated a combination of both these growth patterns. E-cadherin expression was absent in clones 5A, 5C, and 5D and very prominent in clone 5B, when compared to the parental line. The absence of E-cadherin expression correlated with increased invasiveness, as measured in an in vitro invasion assay. Subcutaneous injections of clones 5A, 5C, and 5D yielded lung metastases and no primary tumors at the site of inoculation while clone 5B was tumorigenic and produced fewer lung metastases in vivo. These clones, therefore, provide a potential for studying a variety of molecules involved in prostate cancer invasion and metastasis, especially for the direct testing of the significance of E-cadherin expresssion in prostate cancer progression.