The microenvironment surrounding carcinoma cells influences cell behavior through complex interactions of biochemical factors, matrix architecture and matrix mechanical properties.
Our research focuses on understanding the molecular mechanisms by which the stromal extracellular matrix and stromal cell populations influence epithelial cell behavior in cancer. We are particularly interested in how these factors influence disease progression and resistance to therapeutic intervention in breast and pancreas cancer.
We utilize advanced quantitative imaging, cell and matrix mechanics, tissue-engineered 3D microenvironments, as well as cell and molecular biology techniques. This helps us gain a quantitative understanding of cancer cells' behavior and develop novel technologies and therapeutic strategies for cancer diagnosis and treatment.
Quantitative cancer biology
Advanced optical imaging/biophotonics
Ray A, Lee O, Win Z, Edward RM, Alford PW, Kim DH, Provenzano PP Anisotropic forces from spatially constrained focal adhesions mediate contact guidance directed cell migration. Nature Communications 8:14923, 2017.
Ray A, Slama ZM, Morford RK, Madden SA, Provenzano PP Enhanced Directional Migration of Cancer Stem Cells in 3D Aligned Collagen Matrices, Biophysical Journal, 112(5):1023-1036, 2017.
Nam KH, Kim P, Wood D, Kwon S, Provenzano PP*, Kim DH*, Multiscale Cues Drive Collective Cell Migration, *Co-senior / corresponding authors Scientific Reports 6(29749), 2016.
DuFort CC, DelGiorno KE, Carlson M, Osgood RJ, Zhao C, Huang Z, Shepard MH, Thompson CB, Conner RJ, Thanos CD, Brockenbrough S, Provenzano PP, Frost GI, Shepard MH, Hingorani SR Interstitial pressure in pancreatic ductal adenocarcinoma is dominated by a gel-fluid phase Biophysical Journal 110(9):2106-19, 2016.
Provenzano PP, Cuevas C, Chang AE, Von Hoff DD, Hingorani, SR, Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma, Cancer Cell, 21(3), 418-429, 2012.
Kim DH, Provenzano PP, Smith CL, Levchenko A, Understanding the role of nanotopographic cues in controlling cell functions, Journal of Cell Biology (review), 197(3), 351-60, 2012.
Provenzano PP, Keely PJ, Mechanical signaling through the cytoskeleton regulates cell proliferation by coordinated focal adhesion and Rho GTPase singaling, Journal of Cell Science (review) 124(8), 1195-1205, 2011.
Conklin MW, Eickhoff JC, Riching KM, Pehlke CA, Eliceiri KW, Provenzano PP, Friedl A, Keely PJ, Aligned collagen is a prognostic signature for survival in human breast carcinoma, American Journal of Pathology, 178(3): 1221-1232, 2011.
Provenzano PP, Eliceiri KW, Keely PJ, Shining new light on 3D motility and the metastatic process, Trends in Cell Biology (review) 19(11): 638-648, 2009.
Provenzano PP, Inman DR, Eliceiri KW, Keely PJ, Matrix density-induced stiffness regulates breast cell phenotype, signaling, and gene expression through a FAK-ERK linkage, Oncogene 28(49): 4326-4343, 2009.
Rueden CT, Conklin MW, Provenzano PP, Keely PJ, Eliceiri KW, Nonlinear optical microscopy and computational analysis of intrinsic signatures in breast cancer, Proc IEEE Eng. Med. Biol. Soc. 4077-4090, 2009.
Provenzano PP, Inman DR, Eliceiri KW, Keely PJ, Multiphoton microscopy and fluorescence lifetime imaging microscopy (FLIM) to monitor metastasis and the tumor microenvironment, Clinical & Experimental Metastasis – Special Issue: Imaging the Dynamics of Cancer (invited review) 26(4): 357-70, 2009.
Conklin MW, Provenzano PP, Eliceiri KW, Sullivan R, Keely PJ, Fluorescence lifetime imaging of endogenous fluorophores in histopathology sections reveals differences between normal and tumor epithelium in carcinoma in situ of the breast, Cell Biochemistry and Biophysics, 53(3): 145-157, 2009.
Provenzano PP, Inman DR, Trier SM, Eliceiri KW, Keely PJ, Contact guidance mediated 3D cell migration is regulated by Rho/ROCK-dependent matrix reorganization, Biophysical Journal, 95: 5374-5384, 2008.
Provenzano PP, Inman DR, Eliceiri KW, Beggs HE, Keely PJ, Mammary epithelial-specific disruption of focal adhesion kinase retards tumor formation and metastasis in a transgenic mouse model of human breast cancer, American Journal of Pathology, 173(5): 1551-1565, 2008.
Provenzano PP, Rueden CT, Trier SM, Yan L, Ponik SM, Inman DR, Keely PJ, and Eliceiri KW, Nonlinear optical imaging and spectral-lifetime computational analysis of endogenous and exogenous fluorophores in breast cancer, Journal of Biomedical Optics, 13(3): 031220, 2008.
Provenzano PP, Eliceiri KW, Campbell JW, Inman DR, White JG, Keely PJ, Collagen reorganization at the tumor-stromal interface facilitates local invasion, BMC Medicine 34(1): 2006.