Mechanisms of metastatic spread of high aggressive tumors such as small cell lung cancer (SCLC) are poorly understood. A unique SCID-hu metastasis model was developed that for the first time allows metastasis of SCLC to be studied in the experimental in vivo setting. Molecular analysis of SCLC cell lines with different metastatic potentials have led to the identification of a novel human gene designated CC3 whose expression is lacking in metastatic cells. Introduction of CC3 into SCLC cells suppresses their ability to form metastatic tumors in the SCID-hu mice. The goal of this project then is to prove that CC3 is a metastasis suppressor gene in small cell lung cancer and to analyze the mechanisms of metastasis suppression by CC3. The functional relevance of the lack of expression of CC3 to the metastatic phenotype of SCLC will be further confirmed in the in vivo metastasis assays. The clinical relevance and potential prognostic significance of CC3 expression will be evaluated through analysis of its expression in clinical tumor specimens. The mechanism of metastasis-suppression by CC3 will be addressed in experiments designed to define the effects of CC3 expression on the phenotype of metastatic cells. These investigators anticipate that the results of these studies will advance the understanding of the mechanisms of metastasis of SCLC. Lack of CC3 protein could have prognostic significance in patients diagnosed with SCLC and potentially other tumors. A thorough understanding of CC3 function might eventually lead to the development of new anti-metastatic therapies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
7R01CA071422-03
Application #
2700684
Study Section
Pathology B Study Section (PTHB)
Program Officer
Mohla, Suresh
Project Start
1998-05-01
Project End
2000-04-30
Budget Start
1998-07-15
Budget End
1999-04-30
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
NicAmhlaoibh, R; Shtivelman, E (2001) Metastasis suppressor CC3 inhibits angiogenic properties of tumor cells in vitro. Oncogene 20:270-5
Whitman, S; Wang, X; Shalaby, R et al. (2000) Alternatively spliced products CC3 and TC3 have opposing effects on apoptosis. Mol Cell Biol 20:583-93
Liu, Y; Thor, A; Shtivelman, E et al. (1999) Systemic gene delivery expands the repertoire of effective antiangiogenic agents. J Biol Chem 274:13338-44
Shtivelman, E (1997) A link between metastasis and resistance to apoptosis of variant small cell lung carcinoma. Oncogene 14:2167-73