Invasive and Metastatic Potential of a v-Ha-ras-Transformed Human Bronchial Epithelial Cell Line

Abstract

The in vivo growth behavior and invasive potential of normal and "immortalized" human bronchial epithelial cells were studied by xenotransplantation procedures, an in vitro assay of invasiveness, and determinations of type IV collagenase activity and mRNA expression. BEAS-2B cells, immortalized after hybrid virus infection (adenovirus 12-simian virus 40), reconstituted a columnar epithelium when xenotransplanted into de-epithelialized rat tracheas transplanted sc into athymic BALB/c mice. A few adenomatous growths could be seen 16 weeks after transplantation. BZR cells, obtained by transfer of the v-Ha-ras oncogene into BEAS-2B cells, were tumorigenic in this xenotransplantation model. BZR-T33 cells, obtained from a tumor produced after injection of BZR cells, were also tumorigenic; however, they exhibited a shorter latent period. When these same cell lines were injected sc and iv into athymic BALB/c mice, BEAS-2B cells were not tumorigenic, and the BZR-T33 cells were more tumorigenic than the BZR cells. The incidence of spontaneous metastases after sc inoculation was zero for BEAS-2B cells, 33% for BZR cells, and 100% for BZR-T33 cells. Similar increasing values that correlated well with the data on in vivo growth were noted in the in vitro invasion assay, the collagenolytic ability, and the mRNA expression of type IV collagenase. Normal human bronchial epithelial cells showed the lowest values in all the assays. These progressive changes occurring in cells derived from the same parental line indicate that the presence of the v-Ha-ras oncogene in immortalized bronchial cells is associated with a full-fledged malignant phenotype, which is further enhanced by in vivo passaging.

Expression of a disintegrin and metalloprotease (ADAM and ADAMTS) enzymes in human non-small-cell lung carcinomas (NSCLC)

“…In sharp contrast, ADAM-12 was strongly expressed in two cell lines, BZR and BZR-T33, derived from BEAS-2B cells by infection with recombinant retrovirus Zip-neo-v-Ha-ras or derived from a tumour formed by BZR cells injected subcutaneously into nude mouse, respectively. These two cell lines expressing ADAM-12 (BZR and BZR-T33) have been reported to display a more invasive behaviour when implanted in mice (Bonfil et al, 1989) than cells not expressing ADAM-12 (BEAS-2B; 16-HBE). ADAM with TS-like motifs-1 (ADAMTS-1) mRNA expression was also investigated in these cell lines ( Figure 1D).…”

Loss of RhoB Expression in Human Lung Cancer Progression

“…The putative tumor-suppressive effect of RhoB in human tumors and the importance of other closely related proteins such as Ras in lung carcinogenesis (23,24) prompted us to study the role of RhoB in lung oncogenesis. To this end, we analyzed RhoB expression in human lung tissue ranging from normal to invasive carcinoma from different histological types, and we showed in two independent studies that RhoB expression decreases with lung cancer progression.…”

Development of a three-dimensional model of lung cancer using cultured transformed lung cells

“…Ideally, cellbased lung models should reproduce the structural organization, multicellular complexity, differentiation state, and function of the human respiratory epithelium. Immortalized human epithelial cell lines, such as BEAS-2B, 18 transformed human epithelial cell lines resulting in a malignant phenotype (BZR-T33), 52 primary normal human bronchial epithelial (NHBE) cells, 53 and primary human carcinomas are used to study pathobiology and therapeutic interventions in lung cancer. Traditional monolayer cultures (2-D) of immortalized human broncho-epithelial (HBE) cells and transformed cells represent homogenous lineages, is convenient with high proliferation rates.…”