Differential mechanisms of tumor progression in clones from a single heterogeneous human melanoma
Croteau, W; Jenkins, MH; Ye, S; Mullins, DW; Brinckerhoff, CE
| HERO ID | 2902791 |
|---|---|
| In Press | No |
| Year | 2013 |
| Title | Differential mechanisms of tumor progression in clones from a single heterogeneous human melanoma |
| Authors | Croteau, W; Jenkins, MH; Ye, S; Mullins, DW; Brinckerhoff, CE |
| Journal | Journal of Cellular Physiology |
| Volume | 228 |
| Issue | 4 |
| Page Numbers | 773-780 |
| Abstract | We used vertical growth phase (VGP) human VMM5 melanoma cells to ask whether the tumor microenvironment could induce matrix metalloproteinase-1 (MMP-1) in vivo, and whether this induction correlated with metastasis. We isolated two clones from parental VMM5 cells: a low MMP-1 producing clone (C4) and high producing clone (C9). When these clones were injected orthotopically (intradermally) into nude mice, both were equally tumorigenic and produced equivalent and abundant amounts of MMP-1. However, the tumors from the C4 clones displayed different growth kinetics and distinct profiles of gene expression from the C9 population. The C4 tumors, which had low MMP-1 levels in vitro, appeared to rely on growth factors and cytokines in the microenvironment to increase MMP-1 expression in vivo, while MMP-1 levels remained constant in the C9 tumors. C9 cells, but not C4 cells, grew as spheres in culture and expressed higher levels of JARID 1B, a marker associated with melanoma initiating cells. We conclude that VMM5 melanoma cells exhibit striking intra-tumor heterogeneity, and that the tumorigenicity of these clones is driven by different molecular pathways. Our data suggest that there are multiple mechanisms for melanoma progression within a tumor, which may require different therapeutic strategies. |
| Doi | 10.1002/jcp.24225 |
| Pmid | 23001823 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |