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 (US)
Pages (from-to)381-393
Number of pages13
JournalACS Central Science
Volume3
Issue number5
DOIs
StatePublished - May 24 2017

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Stem cells
Cells
Peptides
Proteoglycans
Substrates
Tumors
Ligands
Proteins
Microarrays
Screening
Bone
Adhesion
Chemical activation
Molecules
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Chemical Engineering(all)
  • Chemistry(all)

Cite this

Combinatorial Discovery of Defined Substrates That Promote a Stem Cell State in Malignant Melanoma. / Zhang, Douglas; Lee, Junmin; Sun, Michael B.; Pei, Yi; Chu, James; Gillette, Martha U.; Fan, Timothy M.; Kilian, Kristopher A.

In: ACS Central Science, Vol. 3, No. 5, 24.05.2017, p. 381-393.

Research output: Contribution to journalArticle

Zhang, Douglas ; Lee, Junmin ; Sun, Michael B. ; Pei, Yi ; Chu, James ; Gillette, Martha U. ; Fan, Timothy M. ; Kilian, Kristopher A. / Combinatorial Discovery of Defined Substrates That Promote a Stem Cell State in Malignant Melanoma. In: ACS Central Science. 2017 ; Vol. 3, No. 5. pp. 381-393.
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