During the previous period of support we established 25 human colon carcinoma cell lines from 20 primary tumor specimens. The cell lines had diverse biological properties which were reflective of the inter and intratumoral heterogeneity associated with this disease in humans. The cell lines were divided into 3 groups on the basis of biological and biochemical properties. Group I was highly aggressive and undifferentiated while Group III lines were relatively indolent and differentiated. Group II lines had intermediate properties. Transforming growth factors (TGF) and factors which inhibited anchorage independent growth (TIF) of malignant cells were isolated from a Group II colon carcinoma cell line. These factors showed selective activity towards Group III (TGF and TIF) and Group II (TIF) lines, but had no activity with Group I lines. These results suggest that the heterogeneity of human colon carcinoma is due at least in part to the ability to express or respond to a specific balance of endogenous stimulatory and inhibitory factors. In other work utilizing model systems of malignant mouse cells with well-characterized growth controls involving TGF's we showed that differentiation agents like N,N-dimethylformamide (DMF) and retinoic acid (RA) eliminate RGF sensitivity and alter growth factor expression while re-establishing normal growth controls to the treated malignant cells. During the next period of support we propose to determine the relationship between the biological phenotype of colonic carcinoma cells and growth factors. The types of factors produced by each of the groups will be determined. The sensitivity of the groups to each factor isolated will be determined. Finally, the modulation of the biological properties of colon carcinoma cell lines by DMF, RA and TIF will be related to alterations in factor expression and/or sensitivity.

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National Cancer Institute (NCI)
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Pathology B Study Section (PTHB)
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Baylor College of Medicine
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Leiphrakpam, Premila D; Agarwal, Ekta; Mathiesen, Michelle et al. (2014) In vivo analysis of insulin-like growth factor type 1 receptor humanized monoclonal antibody MK-0646 and small molecule kinase inhibitor OSI-906 in colorectal cancer. Oncol Rep 31:87-94
Leiphrakpam, Premila D; Rajput, Ashwani; Mathiesen, Michelle et al. (2014) Ezrin expression and cell survival regulation in colorectal cancer. Cell Signal 26:868-79
Agarwal, Ekta; Chaudhuri, Anathbandhu; Leiphrakpam, Premila D et al. (2014) Akt inhibitor MK-2206 promotes anti-tumor activity and cell death by modulation of AIF and Ezrin in colorectal cancer. BMC Cancer 14:145
Chowdhury, Sanjib; Ongchin, Melanie; Sharratt, Elizabeth et al. (2013) Intra-tumoral heterogeneity in metastatic potential and survival signaling between iso-clonal HCT116 and HCT116b human colon carcinoma cell lines. PLoS One 8:e60299
Agarwal, Ekta; Brattain, Michael G; Chowdhury, Sanjib (2013) Cell survival and metastasis regulation by Akt signaling in colorectal cancer. Cell Signal 25:1711-9
Zou, Yi; Howell, Gillian M; Humphrey, Lisa E et al. (2013) Ron knockdown and Ron monoclonal antibody IMC-RON8 sensitize pancreatic cancer to histone deacetylase inhibitors (HDACi). PLoS One 8:e69992
Wang, Jing; Rajput, Ashwani; Kan, Julie L C et al. (2009) Knockdown of Ron kinase inhibits mutant phosphatidylinositol 3-kinase and reduces metastasis in human colon carcinoma. J Biol Chem 284:10912-22
Sawhney, Rajinder S; Liu, Wensheng; Brattain, Michael G (2009) A novel role of ERK5 in integrin-mediated cell adhesion and motility in cancer cells via Fak signaling. J Cell Physiol 219:152-61
Li, Fengzhi; Brattain, Michael G (2006) Role of the Survivin gene in pathophysiology. Am J Pathol 169:1-11