Influence of the host microenvironment on the clonal selection of human colon carcinoma cells during primary tumor growth and metastasis.

摘要: The purpose of this study was to determine the subpopulation dynamics human colon carcinoma (HCC) cells growing at orthotopic (cecum, liver) or ectopic (subcutis, kidney, spleen) sites in nude mice and correlate any outgrowth distinct clones with differential expression metastasis-related genes. Low metastatic KM12C HCC were genetically tagged a retrovirus harboring neomycin-resistance (Neo) gene. Southern blot analyses demonstrated only minor resolution Neo hybridization pattern DNA isolated from primary tumors orthotopically ectopically, suggesting polyclonal outgrowth. In contrast, major observed liver-specific metastases, demonstrating single dominant clones. Expression epidermal growth factor receptor (EGR-R) increased 20–60% liver metastases vs spleen cells. Transforming alpha (TGF-α), amphiregulin (AR), c-met showed modest differences mRNA expression. A 20–80% increase type IV collagenase levels also all tumor specimens. Furthermore, multi-drug resistance gene PGY-1 carcino-embryonic antigen (CEA) elevated compared cultured Transcript angiogenic factors interleukin-8 basic fibroblast did not clonal These data demonstrate correlation between EGF-R, collagenase, CEA, production metastases. Our results suggest that differentially expressing specific transcripts for genes are forerunners experimental lesions.