Faculty Summaries
Edna Cukierman, PhD
Edna Cukierman, PhD
Associate Professor
Edna.Cukierman@fccc.edu
Office Phone: 215-214-4218
Lab Phone: 215-214-4219
Fax: 215-728-3616
Office: W428
Twitter: @ednacukierman
Fibroblastic Tumor-Associated Stroma and its 3D Extracellular Matrix

In order to develop new approaches for treatment of aggressive cancers, it is necessary to attain a better understanding of their development and progression. One poorly studied aspect of tumorigenesis is the nature of tumor-stromal interactions. It has become clear that the tumor microenvironment (including stromal fibroblasts, infiltrating immune and inflammatory cells, blood and lymphatic vascular network, and the extracellular matrix) is an integral part of the carcinogenic process promoting cell growth and metastases. Benign epithelial tumors are constrained by a surrounding stroma consisting of fibroblastic cells and a fibrillar three-dimensional extracellular matrix. These ‘normal’ fibroblasts and their matrices assist in maintaining a homeostatic equilibrium, exerting an inhibitory effect on the epithelial cells undergoing malignant changes. However, tumor-generated paracrine signaling alters and overcomes this stromal barrier, inducing changes in the local mesenchymal microenvironment that promote rather than impede tumor progression.

In our laboratory, we isolate primary fibroblasts from various murine and human cancers at different stages of tumorigenesis. Using these fibroblasts, we have developed a three-dimensional in vivo-like stromal system, which is used to conduct our studies. Research is directed at better understanding the role of tumor-associated stroma in cancer invasion and metastasis. We aim to understand how tumor cells alter the local mesenchymal microenvironment, at both primary and secondary (e.g., metastatic) niches, in a way that this stroma supports and incites (instead of constraining) tumor progression (e.g., cancer cell invasion). Our group also uses this three-dimensional culturing system as an approach to improve the preclinical cancer drug-development process, believing that stromal microenvironment can significantly alter the efficacy of drugs in evaluation or currently in use for cancer treatment. For this, our laboratory is carrying out analyses that incorporate biochemical, molecular and cell biology assays, laser scanning confocal and real time microscopy, digital analyses, as well as tissue patterning approaches.

Description of research projects
Selected Publications
  1. Håkanson M, Kobel S, Lutolf MP, Textor M, Cukierman E*, Charnley M*. Controlled Breast Cancer Microarrays for the Deconvolution of Cellular Multilayering and Density Effects upon Drug Responses. PLoS ONE 2012;7(6): e40141. doi:10.1371/journal.pone.0040141 (*co-corresponding author). PLoS ONE
  2. Gupta V, Bassi DE, Simons JD, Devarajan K, Al-Saleem T, Uzzo RG, Cukierman E. Elevated expression of stromal palladin predicts poor clinical outcome in renal cell carcinoma. PLoS One. 2011;6(6):e21494. Epub 2011 Jun 28. PubMed
  3. Goetz JG, Minguet S, Navarro-Lérida I, Lazcano JJ, Samaniego R, Calvo E, Tello M, Osteso-Ibáñez T, Pellinen T, Echarri A, Cerezo A, Klein-Szanto AJ, Garcia R, Keely PJ, Sánchez-Mateos P, Cukierman E, Del Pozo MA. Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis. Cell. 2011 Jul 8;146(1):148-63. PubMed
  4. Lee HO, Mullins SR, Franco-Barraza J, Valianou M, Cukierman E*, Cheng JD*. FAP-overexpressing fibroblasts produce an extracellular matrix that enhances invasive velocity and directionality of pancreatic cancer cells. BMC Cancer. 2011 Jun 13;11(1):245. (* co-corresponding author). PubMed
  5. Kwon Y, Cukierman E*, Godwin AK*. Differential expressions of adhesive molecules and proteases define mechanisms of ovarian tumor cell matrix penetration/invasion. PLoS One. 2011 Apr 19;6(4):e18872. (* co-corresponding author). PubMed
  6. Castelló-Cros R, Khan DR, Simons J, Valianou M, Cukierman E. Staged stromal extracellular 3D matrices differentially regulate breast cancer cell responses through PI3K and beta1-integrins. BMC Cancer. 2009 Mar 26;9:94. PubMed
  7. Serebriiskii I, Castello-Cros R, Lamb A, Golemis EA, and Cukierman E. Fibroblast-derived 3D matrix differentially regulates the growth and drug-responsiveness of human cancer cells. Matrix Biology. 2008;27:573-585. PubMed
  8. Amatangelo MD, Bassi DE, Klein-Szanto AJ, Cukierman E. Stroma-derived three-dimensional matrices are necessary and sufficient to promote desmoplastic differentiation of normal fibroblasts. Am J Pathol. 2005;167(2):475-88. PubMed
  9. Cukierman E, Pankov R, Stevens DR, and Yamada KM. Taking cell-matrix adhesions to the third dimension. Science. 2001;294:1708-1712. PubMed
All publications