James McCarthy, PhD

Professor, Department of Laboratory Medicine and Pathology

James McCarthy

Contact Info

mccar001@umn.edu

Office Phone 612-625-7454

Fax 612-626-2696

Mailing Address:
MMC 609 Mayo
8609
420 Delaware SE
Minneapolis, MN 55455

Professor, Department of Laboratory Medicine and Pathology

Program co-Leader, Tumor Microenvironment, Masonic Cancer Center (MCC)


University of Minnesota (Laboratory Medicine and Pathology), 1981-1983

PhD, Catholic University of America, Washington, D.C., 1981

Susquehanna University, Selinsgrove, PA, 1974

Summary

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.

Research

Publications

Turley, EA, Wood DK and McCarthy JB. "Carcinoma cell hyaluronan as a "portable" cancerized prometastatic microenvironment." Cancer Res 2016 76(9): 2507-2512.

Schwertfeger KL, Cowman MK, Telmer PG, Turley EA, McCarthy JB. Hyaluronan, Inflammation, and Breast Cancer Progression.  Front Immunol. 2015 Jun 8;6:236. doi: 10.3389/fimmu.2015.00236. eCollection 2015. Review.

Tolg, C., Hamilton, S.R. Nakrieko,K.A., Kooshesh, F., Walton, P., McCarthy, J.B., Bissell, M.J. and Turley, E.A. 2006. Rhamm-/- fibroblasts are defective in CD44-mediated ERK1,2 motogenic signaling, leading to defective skin wound repair. J Cell Biol 175(6): 1017-28.

Iida, J., Wilhelmson, K.L., Ng, J., Morrison, C., Tam, E. Overall, C.M. and McCarthy, J.B. 2007. Chondroitin Sulfate Enhances Pro-MMP-2 (Progelatinase A) Activaiton by Membrane-Type Matrix Metalloproteinase (MT3-MMP) In Vitro. Biochem. J.403(3):553-63. PubMed PMID: 17217338; PubMed Central PMCID: PMC1876388.

Hamilton SR, Fard SF, Paiwand FF, Tolg C, Veiseh M, Wang C, McCarthy JB, Bissell MJ, Koropatnick J, Turley EA. The hyaluronan receptors CD44 and Rhamm (CD168) form complexes with ERK1,2 that sustain high basal motility in breast cancer cells. J Biol Chem. 2007 282(22):16667-80. PubMed Central PMCID: PMC2949353.

Yang JB, McCarthy JB. Syntenin: a novel PDZ domain-containing scaffolding protein associated with human melanoma metastasis. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2007 Apr;32(2):204-12. Review. PubMed PMID: 17478924.

Iida J, McCarthy JB. Expression of collagenase-1 (MMP-1) promotes melanoma growth through the generation of active transforming growth factor-beta. Melanoma Res. 2007 Aug;17(4):205-13. PubMed PMID: 17625450.

Yang J, Price MA, Li GY, Bar-Eli M, Salgia R, Jagedeeswaran R, Carlson JH, Ferrone S, Turley EA, McCarthy JB. Melanoma proteoglycan modifies gene expression to stimulate tumor cell motility, growth, and epithelial-to-mesenchymal transition. Cancer Res. 2009 Oct 1;69(19):7538-47. Epub 2009 Sep 8. PubMed PMID: 19738072; PubMed Central PMCID: PMC2762355.

Wang, X., Osada, T., Wang, Y., Yu, L., Sakakura ,K., Katayama, A., McCarthy, J.B., Brufsky, A., Chivukula, M., Khoury, T., Hsu, D.S., Barry, W.T., Lyerly, H.K., Clay, T.M., Ferrone, S. 2010. CSPG4 protein as a new target for the antibody-based immunotherapy of triple-negative breast cancer. J. Natl. Cancer Inst. 102:1496-512. PMCID: PMC2950168

Invited Reviews -

Price, M.A., Colvin Wanshura, L.E., Yang, J., Carlson, J., Xiang, B., Li, G., Ferrone, S., Dudek, A.Z., Turley, E.A., McCarthy, J.B. CSPG4, a potential therapeutic target, facilitates malignant progression of melanoma. Pigment Cell Melanoma Res. 2011; 24:1148-57. PMCID: PMC3426219

Tolg, C., McCarthy J., Yazdani, A., Turley, E A. 2014. Hyaluronan and RHAMM in Wound Repair and the ‘Cancerization’ of Stromal Tissue. Biomed Res Int. 2014;2014:103923. doi: 10.1155/2014/103923. Epub 2014 Aug 4. PMID: 25157350 [PubMed - in process] PMCID: PMC4137499

Schwertfeger, K.L., Cowman, M.K, Telmer, P.G. Turley, E.A and McCarthy, J.B. 2015. Hyaluronan, Inflammation, and Breast Cancer Progression. 2015. Front Immunol. Jun 8;6:236. doi: 10.3389/fimmu.2015.00236. eCollection 2015 PMID: 26106384 [PubMed] PMCID: PMC4459097

Cowman, M.K., Lee, H.G. Schwertfeger, K.L., McCarthy, J.B., Turley, E.A. 2015. The Content and Size of Hyaluronan in Biological Fluids and Tissues. Front. Immunol. Jun 2;6:261. Doi10.3389/fimmu.2015.00261. eCollection 2015. PMID: 26082778 [PubMed] PMCID: PMC4451640

Complete list of published works listed in PubMed:

http://www.ncbi.nlm.nih.gov/pubmed/?term=McCarthy, J.B.