Combinatorial Discovery of Defined Substrates That Promote a Stem Cell State in Malignant Melanoma
| Autor: | Kristopher A. Kilian, James Chu, Michael B. Sun, Junmin Lee, Douglas Zhang, Martha U. Gillette, Timothy M. Fan, Yi Pei |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Tumor microenvironment Cell signaling General Chemical Engineering Proteoglycan binding General Chemistry Biology medicine.disease Stem cell marker Molecular biology 3. Good health Metastasis Cell biology lcsh:Chemistry Extracellular matrix 03 medical and health sciences 030104 developmental biology lcsh:QD1-999 Cancer cell medicine Peptide microarray Research Article |
| Zdroj: | ACS Central Science ACS Central Science, Vol 3, Iss 5, Pp 381-393 (2017) |
| ISSN: | 2374-7951 2374-7943 |
| Popis: | 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. A peptide microarray reveals combinations of surface bound peptides that promote a stem cell-like state in melanoma cells. Proteoglycan mediated adhesion and bone morphogenetic protein signaling are proposed to orchestrate this transformation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|