Browsing by Subject "invasion"

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    Functional characterization of a panel of high-grade serous ovarian cancer cell lines as representative experimental models of the disease.
    (Impact Journals, 2016-05-31) Haley, James; Tomar, Sunil; Pulliam, Nicholas; Xiong, Sen; Perkins, Susan M.; Karpf, Adam R.; Mitra, Sumegha; Nephew, Kenneth P.; Mitra, Anirban K.; Department of Medical and Molecular Genetics, IU School of Medicine
    Genomic analysis of ovarian cancer cell lines has revealed a panel that best represents the most common ovarian cancer subtype, high-grade serous ovarian cancer (HGSOC). However, these HGSOC-like cell lines have not been extensively applied by ovarian cancer researchers to date, and the most commonly used cell lines in the ovarian cancer field do not genetically resemble the major clinical type of the disease. For the HGSOC-like lines to serve as suitable models, they need to be characterized for common functional assays. To achieve that objective, we systematically studied a panel of HGSOC cells CAOV3, COV362, Kuramochi, OVCAR4, OVCAR5, OVCAR8, OVSAHO and SNU119 for migration, invasion, proliferation, clonogenicity, EMT phenotype and cisplatin resistance. They exhibited a range of efficacies and OVCAR5, OVCAR8 and Kuramochi were the most aggressive. SNU119 and OVSAHO cells demonstrated the lowest functional activities. Wide differences in expression of EMT markers were observed between cell lines. SNU119 were the most epithelial and OVCAR8 had the most mesenchymal phenotype. COV362 was the most resistant to cisplatin while CAOV3 was the most sensitive. Taken together, our systematic characterization represents a valuable resource to help guide the application of HGSOC cells by the cancer research community.
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    ITF2 is a target of CXCR4 in MDA-MB-231 breast cancer cells and is associated with reduced survival in estrogen receptor-negative breast cancer
    (Taylor & Francis, 2010-08-15) Appaiah, Hitesh; Bhat-Nakshatri, Poornima; Mehta, Rutika; Thorat, Mangesh; Badve, Sunil; Nakshatri, Harikrishna
    CXCR4, a chemokine receptor, plays an important role in breast cancer growth, invasion, and metastasis. The transcriptional targets of CXCR4 signaling are not known. Microarray analysis of CXCR4-enriched and CXCR4-low subpopulations of the MDA-MB-231 breast cancer cell line, which has a constitutively active CXCR4 signaling network, revealed differential expression of ∼ 200 genes in the CXCR4-enriched subpopulation. ITF2, upregulated in CXCR4-enriched cells, was investigated further. Expression array datasets of primary breast tumors revealed higher ITF2 expression in estrogen receptor negative tumors, which correlated with reduced progression free and overall survival and suggested its relevance in breast cancer progression. CXCL12, a CXCR4 ligand, increased ITF2 expression in MDA-MB-231 cells. ITF2 is a basic helixloop-helix transcription factor that controls the epithelial-to-mesenchymal transition and the function of the ID family (inhibitor-of-differentiation) of transcription factors, such as ID2. ID2 promotes differentiation of breast epithelial cells and its reduced expression in breast cancer is associated with an unfavorable prognosis. Both CXCR4 and ITF2 repressed ID2 expression. In xenograft studies, CXCR4-enriched cells formed large tumors and exhibited significantly elevated lung metastasis. Short interfering RNA against ITF2 reduced invasion of the CXCR4-enriched MDA-MB-231 subpopulation, whereas ITF2 overexpression restored the invasive capacity of MDA-MB-231 cells expressing CXCR4shRNA. Furthermore, overexpression of ITF2 in these cells enhanced tumor growth. We propose that ITF2 is one of the CXCR4 targets, which is involved in CXCR4-dependent tumor growth and invasion of breast cancer cells.