Combinatorial Discovery of Defined Substrates That Promote a Stem Cell State in Malignant Melanoma

Douglas Zhang, Junmin Lee, Michael B. Sun, Yi Pei, James Chu, Martha U. Gillette, Timothy M. Fan, Kristopher A. Kilian

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)

Abstract

The tumor microenvironment is implicated in orchestrating cancer cell transformation and metastasis. However, specific cell-ligand interactions between cancer cells and the extracellular matrix are difficult to decipher due to a dynamic and multivariate presentation of many signaling molecules. Here we report a versatile peptide microarray platform that is capable of screening for cancer cell phenotypic changes in response to ligand-receptor interactions. Using a screen of 78 peptide combinations derived from proteins present in the melanoma microenvironment, we identify a proteoglycan binding and bone morphogenic protein 7 (BMP7) derived sequence that selectively promotes the expression of several putative melanoma initiating cell markers. We characterize signaling associated with each of these peptides in the activation of melanoma pro-tumorigenic signaling and reveal a role for proteoglycan mediated adhesion and signaling through Smad 2/3. A defined substratum that controls the state of malignant melanoma may prove useful in spatially normalizing a heterogeneous population of tumor cells for discovery of therapeutics that target a specific state and for identifying new drug targets and reagents for intervention.

Original languageEnglish
Pages (from-to)381-393
Number of pages13
JournalACS Central Science
Volume3
Issue number5
DOIs
Publication statusPublished - 24 May 2017
Externally publishedYes

Cite this