The development and progression of a malignant tumor is a process which involves several essential interactions with the vasculature. Cells in the primary tumor must attract new blood vessels in order to grow beyond a small spheroid and these vessels then provide a conduit for the exit of cells that may progress to become secondary colonies in nearby or distant organs. Tumor cell that travel via the blood stream to distant organs must again interact with the vasculature in order to escape from the blood stream and invade the tissue at the secondary site. In many cases there is a selectivity between certain types of metastatic tumors and the organs that they preferentially colonize. The goal of this proposal is to examine the interactions between tumor cells and blood vessels that may lead to the colonization of specific organ sites. These interactions include the adhesion of tumor cells to specific adhesive determinants, the migration of tumor cells to specific chemotactic determinants and the modulation of tumor cell growth by organ-specific mitogens or growth inhibitors. The goal of this proposal is to isolate and identify cell adhesion and migration- stimulating molecules that may influence the colonization of lung and liver tissue by metastatic tumor cells. Tumor cell receptors to these adhesion and chemotactic molecules will also be characterized. These adhesive and chemotactic molecules will be isolated from whole tissue and from isolated microvessels using a variety of chromatographic techniques. Antibodies raised against the purified molecules will be used to determine the distribution of these factors within the tissues of interest and to determine their localization relative to the organ vasculature. The isolated factors and the antibodies raised against them will then be used in experiments conducted in vivo to attempt to modulate pre- existing patterns of organ-specific tumor colonization.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA037393-09
Application #
3482390
Study Section
Pathology B Study Section (PTHB)
Project Start
1983-07-01
Project End
1993-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
9
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Olsen, Rachelle R; Chung, Ivy; Zetter, Bruce R (2012) Knockdown of antizyme inhibitor decreases prostate tumor growth in vivo. Amino Acids 42:549-58
Spivey, K A; Chung, I; Banyard, J et al. (2012) A role for collagen XXIII in cancer cell adhesion, anchorage-independence and metastasis. Oncogene 31:2362-72
Holleman, A; Chung, I; Olsen, R R et al. (2011) miR-135a contributes to paclitaxel resistance in tumor cells both in vitro and in vivo. Oncogene 30:4386-98
Patel, Nish; Chatterjee, Sabarni K; Vrbanac, Vladimir et al. (2010) Rescue of paclitaxel sensitivity by repression of Prohibitin1 in drug-resistant cancer cells. Proc Natl Acad Sci U S A 107:2503-8
Feldman, Adam S; Banyard, Jacqueline; Wu, Chin-Lee et al. (2009) Cystatin B as a tissue and urinary biomarker of bladder cancer recurrence and disease progression. Clin Cancer Res 15:1024-31
Banyard, Jacqueline; Barrows, Courtney; Zetter, Bruce R (2009) Differential regulation of human thymosin beta 15 isoforms by transforming growth factor beta 1. Genes Chromosomes Cancer 48:502-9
Mangold, U; Hayakawa, H; Coughlin, M et al. (2008) Antizyme, a mediator of ubiquitin-independent proteasomal degradation and its inhibitor localize to centrosomes and modulate centriole amplification. Oncogene 27:604-13
Banyard, Jacqueline; Hutchinson, Lloyd M; Zetter, Bruce R (2007) Thymosin beta-NB is the human isoform of rat thymosin beta15. Ann N Y Acad Sci 1112:286-96
Everley, Patrick A; Gartner, Carlos A; Haas, Wilhelm et al. (2007) Assessing enzyme activities using stable isotope labeling and mass spectrometry. Mol Cell Proteomics 6:1771-7
Kim, Sonia W; Mangold, Ursula; Waghorne, Carol et al. (2006) Regulation of cell proliferation by the antizyme inhibitor: evidence for an antizyme-independent mechanism. J Cell Sci 119:2583-91

Showing the most recent 10 out of 45 publications