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Welcome to the Morris Lab
Dr. Vince Morris (AB Berkley ; PhD Chicago)
Office: Rm 301A, Health Science Addition
Phone: 519 661-3452
Fax: 519 661-3499
My research examines the mechanisms of cancer metastasis (spread).
Approximately 10% of North American women will develop breast cancer, and that risk keep rising. Among women who develop breast cancer, metastasis is the leading cause of death. It is thus essential that we know as much of this process as is possible. We have characterized three mammary tumor cell lines of recent origin which were originally derived from the same murine precancerous hyperplastic alveolar nodule (D2). We have shown that the three cell lines differ in their invasive, tumorigenic, and metastatic properties, and therefore, may differ in their abilities to fulfil different steps in the metastatic process. Using these cell lines, we have shown an association between high levels of the cysteine proteinase, cathepsin L, mRNA and increased invasiveness and metastatic ability. We are extending these studies to examine the expression of other proteinases which may be involved in metastasis.
Metastasis of tumor cells consists of a series of steps. In the past, most experiments on metastasis have either treated this process as a "black box" or have studied this dynamic process using fixed tissue. In contrast, we have investigated the mechanisms of cancer cell metastasis in organs living mice during the first 2 hours after injection using intravital videomicroscopy. We have shown that cancer cells were arrested due to size restrictions at the inflow side of the microcirculation. During the next two hours many cells become stretched out; however, they maintain their membrane integrity. We also report for the first time that large (> 3 um) fragments become "pinched off" from arrested cells, often within minutes or even seconds of arrest. We have thus used intravital videomicroscopy to clarify the interaction of cancer cells with vessel walls during metastasis. These studies are being extended to later stages of metastasis.
Wylie S, MacDonald IC, Varghese HJ, Schmidt EE, Morris VL , Groom AC, Chambers AF (1999). The matrix metalloproteinase inhibitor batimastat inhibits angiogenesis in liver metastases of B16F1 melanoma cells. Clin Exp Metastasis 17(2):111-7
Chambers AF, MacDonald IC, Schmidt EE, Morris VL , Groom AC (1998-99). Preclinical assessment of anti-cancer therapeutic strategies using in vivo videomicroscopy. Cancer Metastasis Rev 17(3):263-9
Naumov GN, Wilson SM, MacDonald IC, Schmidt EE, Morris VL , Groom AC, Hoffman RM, Chambers AF (1999). Cellular expression of green fluorescent protein, coupled with high-resolution in vivo videomicroscopy, to monitor steps in tumor metastasis. J Cell Sci 112 ( Pt 12):1835-42
Morris VL , Schmidt EE, MacDonald IC, Groom AC, Chambers AF (1997). Sequential steps in hematogenous metastasis of cancer cells studied by in vivo videomicroscopy. Invasion Metastasis 17(6):281-96
Luzzi KJ, MacDonald IC, Schmidt EE, Kerkvliet N, Morris VL , Chambers AF, Groom AC (1998). Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases. Am J Pathol 153(3):865-73
Ho WC, Heinemann C, Hangan D, Uniyal S, Morris VL , Chan BM (1997). Modulation of in vivo migratory function of alpha 2 beta 1 integrin in mouse liver. Mol Biol Cell 8(10):1863-75
Hangan D, Morris VL , Boeters L, von Ballestrem C, Uniyal S, Chan BM (1997). An epitope on VLA-6 (alpha6beta1) integrin involved in migration but not adhesion is required for extravasation of murine melanoma B16F1 cells in liver. Cancer Res 57(17):3812-7