The research interest in my laboratory is the role of stromal fibroblasts and stroma-epithelial interactions in colorectal carcinogenesis. My laboratory has made the important observation that up-regulation of cyclooxygenase-2 expression occurs in the subepithelial stromal layer in the earliest pre-malignant stages of colorectal carcinogenesis.
The over-expression of cyclooxygenase-2 (COX-2) in subepithelial stromal cells contributes to the progression of colorectal adenomas to adenocarcinomas (colorectal cancers, CRC). Interleukin-1b (IL-1b) and deoxycholic acid (DCA) up-regulate colorectal fibroblast COX-2 expression. Our studies seek to understand paracrine effects of fibroblast COX-2 products on colorectal epithelial cells. The goal is to identify new approaches to the prevention and treatment of CRC based on a more complete understanding of carcinogenic stromal-epithelial interactions.
We are developing coculture and transgenic mouse models, respectively, for the in vitro and in vivo study of these interactions.
We are interested in understanding the specific contributions of fibroblast COX-2 expression. Our studies involve using an engineered mouse model in which COX-2 is conditionally deleted only in cells of fibroblast lineage.
Through this work we expect to define better the role of stromal cells in colorectal carcinogenesis and suggest novel therapeutic approaches.
Any link on the below references will take you off
of the BMCB site and to an abstract of that particular paper.
Gerner, E.W., N.A. Ignatenko, P. Lance, and L.H. Hurley. 2005. A comprehensive strategy to combat colon cancer targeting the adenomatous polyposis coli tumor suppressor gene. Annals of the New York Academy of Sciences 1059 :97-105.
Nelson, M.A., A.C. Goulet, E.T. Jacobs, and P. Lance. 2005. Studies into the anticancer effects of selenomethionine against human colon cancer. Annals of the New York Academy of Sciences 1059: 26-32.
Ranger-Moore, J., D. Frank, P. Lance, D. Alberts, M. Yozwiak, H.G. Bartels, J. Einspahr, and P.H. Bartels. Karyometry in rectal mucosa of patients with previous colorectal adenomas. Quantitative Cytology and Histology 27: 134-142.
Alberts, D.S., M.E. Martinez, L.M. Hess, J.G. Einspahr, S.B. Green, A.K. Bhattacharyya, J. Guillen, M. Krutzsch, A.K. Batta, G. Salen, L. Fales, K. Koonce, D. Parish, M. Clouser, D. Roe, and P. Lance P; Phoenix and Tucson Gastroenterologist Networks. Phase III trial of ursodeoxycholic acid to prevent colorectal adenoma recurrence. Journal of the National Cancer Institute 97: 846-853.
Zhu, Y., P. Hua, and P. Lance. 2003. Cyclooxygenase-2 expression and prostanoid biogenesis reflect clinical phenotype in human colorectal fibroblast strains. Cancer Research 63: 522-526.
Zhu, Y., P. Hua, S. Rafiq, E.J. Waffner, M.E. Duffey, and P. Lance. 2002. Ca2+- and PKC-dependent stimulation of PGE2 synthesis by deoxycholic acid in human colonic fibroblasts. Amercan Journal of Physiology Gastrointestinal and Liver Physiology 283: G503-G510.
Lanza, E., A. Schatzkin, C. Daston, D. Corle, L. Freedman, R. Ballard-Barbash, B. Caan, P. Lance, J. Marshall, F. Iber, M. Shike, J. Weissfeld, M. Slattery, E. Paskett, D. Mateski, and P. Albert. 2001. Implementation of a 4-y, high-fiber, high-fruit-and-vegetable, low-fat dietary intervention: results of dietary changes in the Polyp Prevention Trial. American Journal of Clinical Nutrition 74: 387-401.
Zhu, Y., U. Srivatana, A. Ullah, H. Gagneja, C.S. Berenson, and P. Lance. 2001. Suppression of a sialyltransferase by antisense DNA reduces invasiveness of human colon cancer cells in vitro. Biochimica et Biophysica Acta 1536: 148-160.
Schatzkin, A., E. Lanza, D. Corle, L. Freedman, P. Lance, F. Iber, B. Caan, M. Shike, J. Weissfeld, R. Burt, R. Cooper, W. Kikendall, and J. Cahill. 2000. Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group. New England Journal of Medicine 342: 1149-1155.
