Our laboratory is studying the molecular mechanisms of adhesion
of fibroblasts and neuronal cells, as well as their malignant
derivatives, to fibronectin extracellular matrices since these processes
are critical in regulation of gene expression and in the metastatic spread
of tumor cells. Studies are revealing a diversity of mechanisms by which
tumor and particularly metastatic cells adhere and detach from matrices,
as well as the roles of several different cell surface receptors in these
processes. Molecular biological interest has focussed on regulation of
fibronectin and receptor gene expressions for effecting adhesive events
during tumor progression, as well as on the amplification/over-expression
of the N-myc oncogene (for the neural cells) or the Ras oncogene
(for the fibroblasts) as influencing metastasis and for their influence
on matrix adhesion of tumor cell populations. Clonal dominance of highly
selected tumor cell subsets and the earliest events in micrometastasis
formation in target organs are also being evaluated with drug-resistance
genes and three different histochemical marker genes, permitting ultrasensitive
tracking of tumor cells during tumor development and metastasis.
Holleran, J.L., Miller, C.J., Edgehouse, N.L., Pretlow, T.P., and Culp, L.A. Differential experimental micrometastasis to lung, liver, and bone with lacZ-tagged CWR22R prostate carcinoma cells. Clinical Exp. Met., 19: 17-24 (2002). [PubMed]
Culp, L.A., Lin, W.-c., Kogerman, P., Holleran, J.L., and Miller, C.J. Tumor-specific metastasis to lung using reporter-gene tagged tumor cells. In Lung Cancer: Methods and Protocols, Methods in Molecular Medicine Series, Vol. 1, Edited by Barbara Driscoll, Humana Press, Inc., Totowa, N.J., pp. 509-526 (2002).
Culp, L.A., Judware, R., Kogerman, P., Holleran, J.L. and Miller, C.J. matrix and matrix receptors: alterations during tumor progression--update 2000. In Encyclopedia of Cancer, Second Edition, Vol. I, Ed. J.R. Bertino and J. Wang, Academic Press, Inc., San Diego, CA, in press (2002).
Holleran, J.L., Miller, C.J., and Culp, L.A. Tracking micrometastasis to multiple organs with lacZ-tagged CWR22R prostate carcinoma cells. J. Histochem. & Cytochem., 48: 643-651 (2000). [PubMed]
Kogerman, P., Sy, M.-S., and Culp, L.A. Over-expressed human CD44s promotes lung colonization during micrometastasis of murine fibrosarcoma cells: facilitated retention in the lung vasculature. Proc. Natl. Accad. USA, 94: 13233-38 (1997). [PubMed]