Mesothelin Binding to CA125/MUC16 Promotes Pancreatic Cancer Cell Motility and Invasion via MMP-7 Activation

Chang, K. & Pastan, I. Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas and ovarian cancers. Proc Natl Acad Sci U S A 93, 136–40 (1996).

Argani, P. et al. Mesothelin is overexpressed in the vast majority of ductal adenocarcinomas of the pancreas: identification of a new pancreatic cancer marker by serial analysis of gene expression (SAGE). Clin Cancer Res 7, 3862–8 (2001).

Hassan, R. et al. Mesothelin is overexpressed in pancreaticobiliary adenocarcinomas but not in normal pancreas and chronic pancreatitis. Am J Clin Pathol 124, 838–45 (2005).

Huang, C. Y. et al. Serum mesothelin in epithelial ovarian carcinoma: a new screening marker and prognostic factor. Anticancer Res 26, 4721–8 (2006).

Johnston, F. M. et al. Circulating mesothelin protein and cellular antimesothelin immunity in patients with pancreatic cancer. Clin Cancer Res 15, 6511–8 (2009).

Li, M. et al. Mesothelin is a malignant factor and therapeutic vaccine target for pancreatic cancer. Mol Cancer Ther 7, 286–96 (2008).

Chang, M. C. et al. Mesothelin enhances invasion of ovarian cancer by inducing MMP-7 through MAPK/ERK and JNK pathways. Biochem J 442, 293–302 (2012).

Servais, E. L. et al. Mesothelin overexpression promotes mesothelioma cell invasion and MMP-9 secretion in an orthotopic mouse model and in epithelioid pleural mesothelioma patients. Clin Cancer Res 18, 2478–89 (2012).

Wang, K. et al. Inhibition of mesothelin as a novel strategy for targeting cancer cells. PLoS One 7, e33214 (2012).

Rump, A. et al. Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion. J Biol Chem 279, 9190–8 (2004).

Gubbels, J. A. et al. Mesothelin-MUC16 binding is a high affinity, N-glycan dependent interaction that facilitates peritoneal metastasis of ovarian tumors. Mol Cancer 5, 50 (2006).

Kaneko, O. et al. A binding domain on mesothelin for CA125/MUC16. J Biol Chem 284, 3739–49 (2009).

O'Brien, T. J. et al. The CA 125 gene: an extracellular superstructure dominated by repeat sequences. Tumour Biol 22, 348–66 (2001).

Kui Wong, N. et al. Characterization of the oligosaccharides associated with the human ovarian tumor marker CA125. J Biol Chem 278, 28619–34 (2003).

Streppel, M. M. et al. Mucin 16 (cancer antigen 125) expression in human tissues and cell lines and correlation with clinical outcome in adenocarcinomas of the pancreas, esophagus, stomach and colon. Hum Pathol 43, 1755–63 (2012).

Haridas, D. et al. Pathobiological implications of MUC16 expression in pancreatic cancer. PLoS One 6, e26839 (2011).

Markman, M., Federico, M., Liu, P. Y., Hannigan, E. & Alberts, D. Significance of early changes in the serum CA-125 antigen level on overall survival in advanced ovarian cancer. Gynecol Oncol 103, 195–8 (2006).

Bast, R. C., Jr et al. CA 125: the past and the future. Int J Biol Markers 13, 179–87 (1998).

Shimizu, A. et al. Coexpression of MUC16 and mesothelin is related to the invasion process in pancreatic ductal adenocarcinoma. Cancer Sci 103, 739–46 (2012).

Einama, T. et al. Co-expression of mesothelin and CA125 correlates with unfavorable patient outcome in pancreatic ductal adenocarcinoma. Pancreas 40, 1276–82 (2011).

Yamamoto, H. et al. Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human pancreatic adenocarcinomas: clinicopathologic and prognostic significance of matrilysin expression. J Clin Oncol 19, 1118–27 (2001).

Bloomston, M., Zervos, E. E. & Rosemurgy, A. S., 2nd Matrix metalloproteinases and their role in pancreatic cancer: a review of preclinical studies and clinical trials. Ann Surg Oncol 9, 668–74 (2002).

Gress, T. M. et al. Expression and in-situ localization of genes coding for extracellular matrix proteins and extracellular matrix degrading proteases in pancreatic cancer. Int J Cancer 62, 407–13 (1995).

Crawford, H. C., Scoggins, C. R., Washington, M. K., Matrisian, L. M. & Leach, S. D. Matrix metalloproteinase-7 is expressed by pancreatic cancer precursors and regulates acinar-to-ductal metaplasia in exocrine pancreas. J Clin Invest 109, 1437–44 (2002).

Fukushima, H. et al. Association of matrilysin mRNA expression with K-ras mutations and progression in pancreatic ductal adenocarcinomas. Carcinogenesis 22, 1049–52 (2001).

Jones, L. E., Humphreys, M. J., Campbell, F., Neoptolemos, J. P. & Boyd, M. T. Comprehensive analysis of matrix metalloproteinase and tissue inhibitor expression in pancreatic cancer: increased expression of matrix metalloproteinase-7 predicts poor survival. Clin Cancer Res 10, 2832–45 (2004).

Chen, S. H., Dallas, M. R., Balzer, E. M. & Konstantopoulos, K. Mucin 16 is a functional selectin ligand on pancreatic cancer cells. FASEB J 26, 1349–59 (2012).

Balzer, E. M. et al. Physical confinement alters tumor cell adhesion and migration phenotypes. FASEB J 26, 4045–56 (2012).

Tong, Z. et al. Chemotaxis of cell populations through confined spaces at single-cell resolution. PLoS One 7, e29211 (2012).

Veit, C. et al. Activation of phosphatidylinositol 3-kinase and extracellular signal-regulated kinase is required for glial cell line-derived neurotrophic factor-induced migration and invasion of pancreatic carcinoma cells. Cancer Res 64, 5291–300 (2004).

Singh, A. K. et al. p38beta MAP kinase as a therapeutic target for pancreatic cancer. Chem Biol Drug Des 80, 266–73 (2012).

Cwik, G., Wallner, G., Skoczylas, T., Ciechanski, A. & Zinkiewicz, K. Cancer antigens 19-9 and 125 in the differential diagnosis of pancreatic mass lesions. Arch Surg 141, 968–73; discussion 974 (2006).

Sato, N. et al. Frequent hypomethylation of multiple genes overexpressed in pancreatic ductal adenocarcinoma. Cancer Res 63, 4158–66 (2003).

Hucl, T. et al. High cancer-specific expression of mesothelin (MSLN) is attributable to an upstream enhancer containing a transcription enhancer factor dependent MCAT motif. Cancer Res 67, 9055–65 (2007).

Sternlicht, M. D. & Werb, Z. How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol 17, 463–516 (2001).

Friedl, P. & Alexander, S. Cancer invasion and the microenvironment: plasticity and reciprocity. Cell 147, 992–1009 (2011).

Remy, L., Trespeuch, C., Bachy, S., Scoazec, J. Y. & Rousselle, P. Matrilysin 1 influences colon carcinoma cell migration by cleavage of the laminin-5 beta3 chain. Cancer Res 66, 11228–37 (2006).

Wroblewski, L. E. et al. Stimulation of MMP-7 (matrilysin) by Helicobacter pylori in human gastric epithelial cells: role in epithelial cell migration. J Cell Sci 116, 3017–26 (2003).

Tan, X. et al. Involvement of matrix metalloproteinase-7 in invasion-metastasis through induction of cell dissociation in pancreatic cancer. Int J Oncol 26, 1283–9 (2005).

Jones, S. et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321, 1801–6 (2008).

Dallas, M. R. et al. Sialofucosylated podocalyxin is a functional E- and L-selectin ligand expressed by metastatic pancreatic cancer cells. Am J Physiol Cell Physiol 303, C616–24 (2012).

Thomas, S. N., Zhu, F., Schnaar, R. L., Alves, C. S. & Konstantopoulos, K. Carcinoembryonic antigen and CD44 variant isoforms cooperate to mediate colon carcinoma cell adhesion to E- and L-selectin in shear flow. J Biol Chem 283, 15647–55 (2008).

Burdick, M. M. & Konstantopoulos, K. Platelet-induced enhancement of LS174T colon carcinoma and THP-1 monocytoid cell adhesion to vascular endothelium under flow. Am J Physiol Cell Physiol 287, C539–47 (2004).

McCarty, O. J., Jadhav, S., Burdick, M. M., Bell, W. R. & Konstantopoulos, K. Fluid shear regulates the kinetics and molecular mechanisms of activation-dependent platelet binding to colon carcinoma cells. Biophys J 83, 836–48 (2002).

Wang, P., Zhu, F., Tong, Z. & Konstantopoulos, K. Response of chondrocytes to shear stress: antagonistic effects of the binding partners Toll-like receptor 4 and caveolin-1. Faseb J 25, 3401–15 (2011).

Zhu, F., Wang, P., Kontrogianni-Konstantopoulos, A. & Konstantopoulos, K. Prostaglandin (PG)D(2) and 15-deoxy-Delta(12,14)-PGJ(2), but not PGE(2), mediate shear-induced chondrocyte apoptosis via protein kinase A-dependent regulation of polo-like kinases. Cell Death Differ 17, 1325–34 (2010).

Thomas, S. N., Schnaar, R. L. & Konstantopoulos, K. Podocalyxin-like protein is an E-/L-selectin ligand on colon carcinoma cells: comparative biochemical properties of selectin ligands in host and tumor cells. Am J Physiol Cell Physiol 296, C505–13 (2009).

Hanley, W. D. et al. Variant isoforms of CD44 are P- and L-selectin ligands on colon carcinoma cells. FASEB J 20, 337–9 (2006).

Napier, S. L., Healy, Z. R., Schnaar, R. L. & Konstantopoulos, K. Selectin ligand expression regulates the initial vascular interactions of colon carcinoma cells: the roles of CD44v and alternative sialofucosylated selectin ligands. J Biol Chem 282, 3433–41 (2007).

Wang, P., Zhu, F. & Konstantopoulos, K. Interleukin-6 synthesis in human chondrocytes is regulated via the antagonistic actions of prostaglandin (PG)E2 and 15-deoxy-Delta(12,14)-PGJ2. PLoS One 6, e27630 (2011).