Research Interest:
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:
1. Role of oxygen as a regulator of tumour cell plasticity and metastatic potential br>
2. Role of embryonic microenvironments n the regulation of stem cell life br>
3. Microenvironmental regulation of placental development at the feto-maternal interface
Selected Publications:
• 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.