Prostaglandin E?2? (PGE?2?) is secreted in high concentrations by a variety of human and animal tumors including the murine Lewis lung carcinoma (LLC). The goal of this study is to determine if PGE?2? could promote tumor metastasis by directly influencing the ability of malignant cells to disseminate from the primary neoplasm to distant sites. Malignant and non-metastatic LLC variants will be isolated and cloned. A radioimmunoassay for quantitating PGE?2? will be used to determine if malignant cells produce more PGE?2? than cells not capable of metastasizing. The in vivo metastatic potentials of the LLC clones will be correlated with their ability to migrate in an in vitro model for the early stages of metastasis: dissemination of malignant cells from a primary neoplasm. With this model, the role of PGE?2? in influencing the migration and presumably the metastatic properties of the tumor cells can be studied in the absence of immune interference in tumor cell survival. The modulation of the malignant properties of cells by PGE?2? will be confirmed in vivo. The results of this study are expected to determine if PGE?2? produced by LLC could promote the early stages of the metastatic process. (M)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
7R01CA045080-01
Application #
3188090
Study Section
Pathology B Study Section (PTHB)
Project Start
1985-09-01
Project End
1988-03-31
Budget Start
1985-09-01
Budget End
1988-03-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Loyola University Chicago
Department
Type
Schools of Medicine
DUNS #
791277940
City
Maywood
State
IL
Country
United States
Zip Code
60153
Walsh, Jarrett E; Young, M Rita I (2011) TGF-beta regulation of focal adhesion proteins and motility of premalignant oral lesions via protein phosphatase 1. Anticancer Res 31:3159-64
Walsh, Jarrett E; Young, M Rita I (2010) Interrelationship between protein phosphatase 1 and TGF-{beta} in regulating motility and cytoskeletal architecture of endothelial cells. Anticancer Res 30:4861-6
Lathers, Deanne M R; Clark, Joseph I; Achille, Nicholas J et al. (2004) Phase 1B study to improve immune responses in head and neck cancer patients using escalating doses of 25-hydroxyvitamin D3. Cancer Immunol Immunother 53:422-30
Romashko, Alex A; Young, M Rita I (2004) Protein phosphatase-2A maintains focal adhesion complexes in keratinocytes and the loss of this regulation in squamous cell carcinomas. Clin Exp Metastasis 21:371-9
Sparano, Anthony; Lathers, Deanne M R; Achille, Nicholas et al. (2004) Modulation of Th1 and Th2 cytokine profiles and their association with advanced head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg 131:573-6
Young, M Rita I; Liu, Shirley W; Meisinger, Jeremy (2003) Protein phosphatase-2A restricts migration of Lewis lung carcinoma cells by modulating the phosphorylation of focal adhesion proteins. Int J Cancer 103:38-44
Banich, James C; Kolesiak, Kristin; Young, M Rita I (2003) Chemoattraction of CD34+ progenitor cells and dendritic cells to the site of tumor excision as the first step of an immunotherapeutic approach to target residual tumor cells. J Immunother 26:31-40
Jackson, Jodi L; Young, M Rita I (2003) Protein phosphatase-2A regulates protein tyrosine phosphatase activity in Lewis lung carcinoma tumor variants. Clin Exp Metastasis 20:357-64
Jackson, Jodi L; Young, M Rita I (2002) Protein phosphatase-2A modulates the serine and tyrosine phosphorylation of paxillin in Lewis lung carcinoma tumor variants. Clin Exp Metastasis 19:409-15
Young, M Rita I; Kolesiak, Kristin; Meisinger, Jeremy (2002) Protein phosphatase-2A regulates endothelial cell motility and both the phosphorylation and the stability of focal adhesion complexes. Int J Cancer 100:276-82

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