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Neurotropic cancers exhibit remarkable affinity for and utilization of the complex neuronatomy of highly innervated organs as a means for primary tumor cell escape. Perineural invasion, or the process of tumor cell migration and invasion along nerves, has been recognized as a major route of tumor cell metastasis for neurotropic cancers including pancreatic, prostate and head and neck. The response of tumor cells to extracellular signals from nerves offers potential for new therapeutic and diagnostic leads for inhibiting metastasis. My research interests are to understand the response of cancer cells to nerve microenvironment signals. The following research areas are investigated in my laboratory:
1. The integrin cell adhesion surface molecules are regulators of cell response to microenvironment signals. The laminin integrin receptors are persistently expressed in progressive epithelial cancers and metastastic disease. The integrin family of receptors are also required for peripheral nervous system development. The current working hypothesis is that the integrin cell adhesion receptors A3B1 and A6B1 direct tumor cell invasion and cellular signaling responses along laminin rich nerves. These studies are executed using an in-vitro tumor and nerve co-culture system modeling the nerve and tumor microenvironment.
2. The extracellular matrix of nerves provides a unique environment which attracts tumor cells. The laminin family of extracellular matrix glycoproteins are necessary for peripheral nerve development and are persistently expressed in nerves associated with actively invading tumor cells. The role of specific nerve associated extracellular matrix proteins (laminin-511 and laminin-411) is tested by examining tumor cell adaptation to and invasion along nerves in the tumor and nerve co-culture system.
3. The relationship between nerves and tumor cells during perineural invasion infers a reciprocal adaptation of tumor and nerve cells within this environment. Expression of neuronal genes is increased in tumor cells possibly exploiting the nerve microenvironment for their metastatic program. Further, nerve cells may institute a similar adaptation to tumor cells by increasing specific genes to increase nerve growth. The gene signatures of tumor and nerve cells in the metastatic environment are being identified. Potential candidates will provide diagnostic or therapeutic leads to directly target the perineural invasion program.
Sroka IC, Pond GD, Nagle RB, Porreca F, Pestano G, Cress AE. Molecular Imaging Candidates Identified in Metastatic Human Prostate Cancer Cells in a Xenograft Model. OPEN Prostate Journal. Online June 2009.
Sroka IC, Chen M, Cress AE. Simplified purification procedure for laminin-332 and laminin-
511 from human cells. Biochemical Biophysical Research Communications. Biochem
Biophys Res Commun. 2008 Oct 24;375(3):410-3.
Pawar SC, King TE, Majuta L, Sroka IC, Wynn D, Nagle RB, Porreca F, Cress AE. The role
of alpha 6 integrin in prostate cancer migration and bone pain in a novel xenograft model.
PLOS One. 2008;3(10):e3535
Sroka IC, McDaniel K, Nagle RB, Bowden GT. Differential localization of MT1-MMP in
human prostate cancer tissue: role of IGF-1R in MT1-MMP expression. Prostate. 2008 Apr
Sroka IC, Nagle RB, Bowden GT. Membrane-type 1 matrix metalloproteinase is regulated by sp1
through the differential activation of AKT, JNK, and ERK pathways in human prostate tumor cells.
Neoplasia. 2007 May;9(5):406-17.
Calsoyas I, Stratton MS. Prostate Cancer Screening: A Racial Dichotomy. Archives Internal Medicine. 2004 Sep 27;164(17):1830-2.