Combinatorial Discovery of Defined Substrates That Promote a Stem Cell State in Malignant Melanoma
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:3 |
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| Enthalten in: |
ACS central science - 3(2017), 5 vom: 24. Mai, Seite 381-393 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Douglas [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 27.03.2024 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1021/acscentsci.6b00329 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Sun, Michael B |e verfasserin |4 aut | |
| 700 | 1 | |a Pei, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, James |e verfasserin |4 aut | |
| 700 | 1 | |a Gillette, Martha U |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Timothy M |e verfasserin |4 aut | |
| 700 | 1 | |a Kilian, Kristopher A |e verfasserin |4 aut | |
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