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Differential mechanisms of tumor progression in clones from a single heterogeneous human melanoma

Version 2 2024-06-12, 14:55
Version 1 2015-09-01, 15:27
journal contribution
posted on 2024-06-12, 14:55 authored by W Croteau, MH Jenkins, S Ye, DW Mullins, CE Brinckerhoff
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.

History

Journal

Journal of cellular physiology

Volume

228

Pagination

773-780

Location

Chichester, Eng.

eISSN

1097-4652

Language

eng

Publication classification

C Journal article, C1.1 Refereed article in a scholarly journal

Copyright notice

2012, Wiley-Blackwell

Issue

4

Publisher

Wiley-Blackwell