Colon carcinoma cells induce CXCL11-dependent migration of CXCR3-expressing cytotoxic T lymphocytes in organotypic culture
ABSTRACT Adoptive immunotherapy of cancer patients with cytolytic T lymphocytes (CTL) has been hampered by the inability of the CTL to home into tumors in vivo. Chemokines can attract T lymphocytes to the tumor site, as demonstrated in animal models, but the role of chemokines in T-lymphocyte trafficking toward human tumor cells is relatively unexplored. In the present study, the role of chemokines and their receptors in the migration of a colon carcinoma (CC) patient's CTL toward autologous tumor cells has been studied in a novel three-dimensional organotypic CC culture. CTL migration was mediated by chemokine receptor CXCR3 expressed by the CTL and CXCL11 chemokine secreted by the tumor cells. Excess CXCL11 or antibodies to CXCL11 or CXCR3 inhibited migration of CTL to tumor cells. T cell and tumor cell analyses for CXCR3 and CXCL11 expression, respectively, in ten additional CC samples, may suggest their involvement in other CC patients. Our studies, together with previous studies indicating angiostatic activity of CXCL11, suggest that CXCL11 may be useful as an immunotherapeutic agent for cancer patients when transduced into tumor cells or fused to tumor antigen-specific Ab.
- SourceAvailable from: Samsiddhi Bhattacharjee[Show abstract] [Hide abstract]
ABSTRACT: Altered microRNA (miRNA) expression profiles have been observed in numerous malignancies, including oral squamous cell carcinoma (OSCC). However, their role in disease is not entirely clear. Several genetic aberrations are characteristic of OSCC, with amplification of chromosomal band 11q13 and loss of distal 11q being among the most prevalent. It is not known if the expression levels of miRNAs in these regions are altered or whether they play a role in disease. We hypothesize that the expression of miRNAs mapping to 11q are altered in OSCC because of loss or amplification of chromosomal material, and that this contributes to the development and progression of OSCC. We found that miR-125b and miR-100 are down-regulated in OSCC tumor and cell lines, and that transfecting cells with exogenous miR-125b and miR-100 significantly reduced cell proliferation and modified the expression of target and nontarget genes, including some that are overexpressed in radioresistant OSCC cells. In conclusion, the down-regulation of miR-125b and miR-100 in OSCC appears to play an important role in the development and/or progression of disease and may contribute to the loss of sensitivity to ionizing radiation.Genes Chromosomes and Cancer 07/2009; 48(7):569-82. DOI:10.1002/gcc.20666 · 3.84 Impact Factor
Chapter: Melanoma Model Systems[Show abstract] [Hide abstract]
ABSTRACT: The majority of basic research until now is still performed using two-dimensional (2-D) cell culture studies with tumor cell lines grown in monolayer as models for tissues. However, cancer biologists increasingly recognize that tumor cells kept in monolayer culture poorly represent the behavior of tumors in vivo. Importantly, they do not adequately recapitulate the tumor microenvironment which critically determines tumor cell proliferation, invasive growth, and metastatic spread. More sophisticated model systems are required not only to better understand the biological basis of these processes but also to more effectively evaluate anticancer drug candidates. In Sect. 15.1 we will review the currently available complex in vitro cell culture model systems which are used in melanoma research. In Sect. 15.2 we will describe the spectrum of experimental mouse models that have been developed over the past decades and discuss some of the relevant strengths and weaknesses of the individual approaches. KeywordsMelanoma-Compex model systems-Organotypic skin culture-Spheroid-Transgenic mice01/1970: pages 309-335;
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ABSTRACT: An automatic approach to unsupervised change detection on multisource and multisensor remote sensing images is proposed. Such an approach, unlike classical ones, allows the fusion of different information sources (e.g. optical data, SAR data) in the unsupervised change detection process. The fusion process is carried out according to a consensus theoretic approach by integrating the estimates of statistical terms achieved on the difference images associated with different sensors. The estimates of the statistical terms of each difference image are carried out by using a novel nonparametric and unsupervised techniqueGeoscience and Remote Sensing Symposium, 2000. Proceedings. IGARSS 2000. IEEE 2000 International; 02/2000