Collagen type I expression in experimental anaplastic thyroid carcinoma: Regulation and relevance for tumorigenicity

Abstract

Fibrosis in solid malignancies plays a significant role in tumor pathophysiology. Potential mechanisms for collagen type I deposition in anaplastic thyroid carcinoma (ATC) were investigated using 6 characterized ATC cell lines. Three of these cell lines, which produced collagen type I, had, as a group, a poor tumorigenicity when inoculated in athymic mice. This group of cells generated tumors in 4 of 24 injected animals (17%). Pro-␣1(I) collagen mRNA-expressing carcinoma and stromal cells were interdispersed in the tumors generated by these ATC cells. By contrast, the 3 noncollagen-producing ATC cell lines were all tumorigenic with a tumor take of 60% in the whole group. In the latter tumors, pro-␣1(I) collagen mRNA-expressing cells were confined to the stromal compartment, well delineated from carcinoma cell islets. To study the influence of ATC cells on collagen type I synthesis by fibroblasts, we used AG 1518 diploid human fibroblasts cultured on poly-(2-hydroxyethyl methacrylate) (poly[HEMA])-coated plates. This culture condition allows the study of the effect of collagen mRNA translation in the regulation of collagen type I synthesis. Conditioned media from the 6 ATC cell lines did not influence collagen synthesis. The ATC cell line KAT-4 stimulated fibroblast synthesis of collagen type I when the two cell types were cocultured on poly[HEMA]-coated substrates. Specific inhibitors of PDGF and TGF-␤ reduced the KAT 4 carcinoma cell-induced stimulation of collagen type I synthesis. Our data suggest that collagen type I production by carcinoma cells correlates negatively with tumorigenicity and that the formation of a well-defined stroma is of importance for tumor growth. Furthermore, our data suggest that tumor cells are able to stimulate collagen mRNA translation in stromal fibroblasts in direct cell-cell contact by, at least in part, transferring PDGF or TGF-␤.

The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells

“…Induced genes included MMPs (MMP3, -10, -12, -13) (38). Another category of genes that was greatly overexpressed in transformed PC cells were those encoding adhesion/structure-associated proteins, such as collagen 1 (Col1α1), thymosin β4, and galectin-3, previously reported to be overexpressed in thyroid carcinomas (39)(40)(41)(42). The dual-specificity phosphatase (DUSP6) was also previously identified as a gene upregulated in human PTC samples (41).…”

Production of multiple cytokines and induction of cachexia in athymic nude mice by a new anaplastic thyroid carcinoma cell line

“…Direct comparisons between Thena and these cell lines would be more ideal to conclude these results. The in vivo growth of Thena cells was comparable to other established anaplastic thyroid carcinoma cell lines (Dahlman et al 2002). Nevertheless, none of the published thyroid carcinoma cell lines have been reported to induce cancer cachexia in nude mice.…”

Identification of the collagen type 1 alpha 1 gene (COL1A1) as a candidate survival-related factor associated with hepatocellular carcinoma

“…Although the difference might influence the survival data of each group, some untreatable reasons, like multiple liver metastasis, distant metastasis or sever hepatic dysfunction, might be correlated with recurrences in COL1A1 down-regulated cases. In connection with this result, Dahlman et al [32] reported that there was a tendency toward a negative correlation between the ability to produce collagen type I and tumorigenicity in the xenograft mouse model of anaplastic thyroid cancer cell lines. This is because collagen type I-producing cancer cells separate themselves from surrounding stromal components that are essential for tumor growth.…”