Bidirectional communication between cells and their microenvironment is a hallmark of both cancer progression and embryological development. Indeed, in all physiological instances, cells do not survive autonomously, but rather rely on extracellular cues to direct functions as diverse as proliferation, apoptosis, invasion and differentiation. The past decade has seen an explosion of research on cells with the capacity to differentiate in response to specific microenvironmental cues. During embryogenesis, these "stem cells" are the source of all cell lineages and in adulthood they function in tissue repair and rejuvenation. Recent studies have found that cancers may similarly develop from stem cell populations, and that these rarely occuring cells care likely responsible for tumour formation, drug resistance and metastasis. The unifying goal of our research program is to determine what types of microenvironments regulate normal and cancer stem cell plasticity and function, and to elucidate the mechanisms by which such microenvironments elicit their effects. Ultimately, these studies will lead to the development of methods to maintain normal stem cell pluripotency and to inhibit cancer cell plasticity and metastasis. This research program is comprised of the following projects:
Role of oxygen as a regulator of tumour cell plasticity and metastatic potential
Role of embryonic microenvironments n the regulation of stem cell life
Microenvironmental regulation of placental development at the feto-maternal interface
Postovit, L-M. , Abbott, D., Payne, S.P., Wheaton, W.W., Margaryan, N.V., Amir, S., Sullivan, R., Innsen, M., Csiszar, K., Hendrix, M.J.C. and Kirschmann, D.A. (2007). Hypoxiareoxygenation: a dynamic regulator of lysyl oxidase facilitated breast cancer migration. Journal of Cellular Biochem. In press.
Hendrix, M.J.C., Seftor, R.E.B., Kaseemeier-Kulesa, J., Kulesa, P.M. and Postovit, L-M. (2007) . Reprogramming metastatic tumour cells with embryonic microenvironments. Nature Cancer Reviews : 7(4): 246-255.
Postovit, L-M., Seftor, E.A., Seftor, R.E.B. and Hendrix, M.J.C. (March 2007). Targeting nodal in malignant melanoma cells. Expert Opinion on Therapeutic Targets: 11(4):497-505.
Postovit, L-M., Costa, F.F., Bischof, J.M., Seftor, E.A., Wen, B., Seftor, R.E.B., Feinberg, A.P., Soares, M.B. and Hendrix, M.J.C. (2007). The commonality of plasticity underlying multipotent tumour cells and embryonic stem cells. J Cell Biochem : 101(4): 908-917.
Postovit, L-M., Seftor, E.A., Seftor, R.E.B. and Hendrix, M.J.C. (2006). Influence of the microenvironment on melanoma cell fate determination and phenotype. Cancer Res : 66: 7833-7836.
Topczewska, J.M.*,Postovit, L-M.*, Margaryan, N.V., Sam, A., Hess, A.R., Wheaton, W.W., Nickoloff, B., Topczewski, J. and Hendrix, M.J.C. (2006). Embryonic and tumorigenic pathways converge via Nodal signaling: Role in melanoma aggressiveness. Nature Medicine : Aug.12(8): 925-932 *Authors contributed equally to work
Postovit, L-M.*, Seftor, E.A.*, Seftor, R.E.B. and Hendrix, M.J.C. (2006). A 3-D model to study the epigenetic effects induced by the microenvironment of human embryonic stem cells. Stem Cells : 24: 501-505 *Authors contributed equally to work
Renaud, S.J., Postovit, L-M., MacDonald-Goodfellow, S.K., McDonald, G.T., Caldwell, J.D. and Graham, C.H. (2006). Activated macrophages inhibit human cytotrophoblast invasiveness in vitro. Biol Reprod : March 30.
Postovit, L-M., Adams, M.A., Lash, G.E., Heaton, J.P.W. and Graham, C.H. (2004). Nitric oxide-mediated regulation of hypoxia-induced B16F10 melanoma metastasis. International J. Cancer : Jan 1; 108(1): 47-53.
Postovit, L-M., Adams, M.A., Lash, G.E., Heaton, J.P. and Graham, C.H. (2002). Oxygen-mediated regulation of tumour cell invasiveness: involvement of a nitric oxide signalling pathway. J. Biol. Chem : Sep 20; 277(38): 35730-35737.
Canning, M.T., Postovit, L-M., Clarke, S.H. and Graham, C.H. (2001). Oxygen-mediated regulation of gelatinase and tissue inhibitor of metalloproteinases-1 expression by invasive cells. Exp. Cell Res. : 267: 88-94.