Dr. McCarthy is a member of the Division of Molecular Pathology and Genomics. His laboratory focuses on understanding the importance of changes in protumorigenic changes in the extracellular matrix (ECM) within cancerized stroma that promote malignant tumor progression. It is well known that cancerized (tumor associated) stroma has an important influence on tumor growth, localized invasion, metastasis and resistance to therapy. These ECM components include stromal associated proteins such as various types of collagens as well as hyaluronan (HA) which is a large tumor-associated polyanionic carbohydrate polymer. The McCarthy laboratory is studying in parallel cell surface receptors for these ECM components used by tumor cells to promote their growth, invasion and metastasis. The receptors that are the focus of these studies are two that bind HA (RHAMM and CD44) as well those that bind specific tumor associated collagens (integrins and CSPG4). These receptors function to organize oncogenic signaling complexes within the plasma membrane of tumor cells. They directly impact on the motility and invasive machinery in tumor cells and they instigate changes in the cancer cell transcriptome to promote progression and metastasis formation. The McCarthy laboratory is currently using specific inhibitory synthetic peptides, novel small molecule inhibitors and immune cell targeting of these receptors as strategies to treat a number of tumor types including prostate, breast, glioblastoma multiforme and melanoma.
Tumor cell adhesion, invasion, metastasis The research in the McCarthy Laboratory focuses on understanding the importance of changes in the relationships between tumor cells and the surrounding extracellular matrix in tumor progression and metastasis. The research in the laboratory is organized into two major areas related to specific tumors. Melanoma, a malignant tumor of the skin, constitutes one of these research focus areas. Ongoing studies in the laboratory address the mechanisms by which an early progression antigen, termed Melanoma Chondroitin Sulfate Proteoglycan (MCSP) enhances adhesion, survival, growth and invasion of primary and metastatic melanomas. MCSP is a transmembrane proteoglycan that can enhance the adhesion and invasion of melanoma cells. Projects related to MCSP-mediated signal transduction, tumor cell survival, and activation of specific proteases important for tumor invasion are currently in progress. Additionally, related studies in prostate cancer are also ongoing in the laboratory. These studies focus on understanding the mechanism by which specific chemotactic cytokines (termed chemokines) stimulate prostate tumor invasion. Research projects are also in progress to study the importance of hyaluronan synthesis in prostate tumor growth, invasion, and metastasis to bone and other organs.
Messam, B., Tolg, C., McCarthy, J., Nelson, A., & Turley, E. (2021). RHAMM Is a Multifunctional Protein That Regulates Cancer Progression. Biomolecules. PubMed Central ID Number: PMC8508827
Tolg C, Messam BJ, McCarthy JB, Nelson AC, Turley EA. Hyaluronan Functions in Wound Repair That Are Captured to Fuel Breast Cancer Progression. Biomolecules. 2021 Oct 20;11(11):1551. doi: 10.3390/biom11111551.
Tolg, C. (Lead Author), Messam, B., McCarthy, J. B., Nelson, A., & Turley, E. (2021) Hyaluronan Functions in Wound Repair That Are Captured to Fuel Breast Cancer Progression. Biomolecules. PubMed Central ID Number: 8615562
Yang, J., Liao*, Q., Price, M., Moriarity, B., Wolf, N., Felices, M., Miller, J., Geller, M., Bendzick, L., Hopps, R., Starr, T., O'Connor, C., Tarullo, S., Nelson, A., Turley, E., Wang, J., & McCarthy, J. (2022) Chondroitin Sulfate Proteoglycan 4, A Targetable Oncoantigen that Promotes Ovarian Cancer Growth, Invasion, Cisplatin Resistance and Spheroid Formation. Translational Oncology. Epub 2021 Dec.20 PMID: 34942534.
Brett, M. E., H. E. Bomberger, G. R. Doak, M. A. Price, J. B. McCarthy and D. K. Wood. "In vitro elucidation of the role of pericellular matrix in metastatic extravasation and invasion of breast carcinoma cells." Integr Biol (Camb) 2018; 10(4): 242-252.
McCarthy, J. B., D. El-Ashry and E. A. Turley. "Hyaluronan, cancer-associated fibroblasts and the tumor microenvironment in malignant progression." Front Cell Dev Biol. 2018; 6: 48.Turley, EA, Wood DK and McCarthy JB. "Carcinoma cell hyaluronan as a "portable" cancerized prometastatic microenvironment." Cancer Res 2016 76(9): 2507-2512.
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