James McCarthy, PhD

Professor and Chairman's Fund Professorship in Cancer Research, Department of Laboratory Medicine and Pathology

James McCarthy

Contact Info

mccar001@umn.edu

Office Phone 612-625-7454

Fax 612-626-2696

Lab Phone 612-625-5453

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

Professor and Chairman's Fund Professorship in Cancer Research, Department of Laboratory Medicine and Pathology

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

Professor, Microbiology, Immunology and Cancer Biology (MICaB) Ph.D. Graduate Program


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

Research Summary/Interests

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.

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

Iida, J., Wilhelmson, K.L., Pei, D., Furcht, L.T., and McCarthy, J.B. 2004. MT1-MMP promotes human melanoma invasion and growth. J. Invest. Dermatol. 122:167-176.

Yang, J., Price, M., Neudauer, C., Xia, H., Simpson, M., and McCarthy, J.B. 2004. Melanoma chondroitin sulfate proteoglycan activates FAK and ERK via separate integrin-dependent mechanisms. J. Cell Biol. 165:881-891.

Kim HR, Wheeler MA, Wilson CM, Iida J, Eng D, Simpson MA, McCarthy JB, Bullard KM. 2004. Hyaluronan facilitates invasion of colon carcinoma cells in vitro via interaction with CD44. Cancer Res. 64(13):4569-76.

Bullard, K. M., Kim, H. R., Wheeler, M. A., Wilson, C. M., Neudauer, C. L., Simpson, M. A., McCarthy, J. B. 2003. Hyaluronan synthase-3 is upregulated in metastatic colon carcinoma cells and manipulation of expression alters matrix retention and cellular growth. Int. J. Cancer. 107: 739-46.

Simpson, M.A., Wilson, C.M., Furcht, L.T., Spicer, A.P., Oegema, T.R., McCarthy, J.B. 2002. Manipulation of hyaluronan synthase expression in prostate adenocarcinoma cells alters pericellular matrix retention and adhesion to bone marrow endothelial cells. J. Biol. Chem. 277:10050-10057.

Simpson, M.A., Wilson, C.M, Furcht, L.T. 2002. Inhibition of prostate tumor hyaluronan synthesis impairs subcutaneous growth and vascularization in immunocompromised mice. Am. J. Path. 161: 849-857.

Iida, J.,Pei, D.,Kang, T.,Simpson, M. A.,Herlyn, M., Furcht, L. T.,McCarthy, J. B. 2001. Melanoma chondroitin sulfate proteoglycan regulates matrix metalloproteinase-dependent human melanoma invasion into type I collagen. J Biol Chem. 276:18786-94.

Simpson, M. A., Reiland, J., Burger, S. R., Furcht, L. T., Spicer, A. P., Oegema, T. R., Jr., McCarthy, J. B. 2001. Hyaluronan synthase elevation in metastatic prostate carcinoma cells correlates with hyaluronan surface retention, a prerequisite for rapid adhesion to bone marrow endothelial cells. J Biol Chem. 276:17949-57.

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.