Candidate regions for testicular cancer susceptibility genes

Although the aetiology of testicular cancer is unknown, a clear familial component has been identified in a number of studies. In an effort to identify susceptibility genes for testicular cancer, the International Testis Cancer Linkage Consortium has been collecting families with multiple cases of testicular cancer. These families have been genotyped for a set of markers across the genome in two separate studies. The family information has also been pooled across the two studies so that the combined evidence can be assessed. While no genomic region gives overwhelming support for a testicular cancer predisposition gene, several regions, notably on chromosomes 3, 5, 12 and 18 show suggestive evidence worthy of further examination. The Consortium is now attempting to identify further families in an attempt to confirm or deny these leads

Three-dimensional co-culture of human monocytes and macrophages with tumor cells: analysis of macrophage differentiation and activation

Here we report on an experimental system for generating TAM in vitro by culturing human MO and MO-derived macrophages (MAC) within 3-dimensional multicellular tumor spheroids (MCS). MO as well as MO-derived MAC migrate into tumor spheroids and spread throughout the entire spheroid within 16 hr. In contrast, fibroblast-spheroids were not infiltrated. The regular expression of MAC maturation-associated antigens on infiltrating MO was suppressed within MCS of the undifferentiated bladder carcinoma line J82 with regard to carboxypeptidase M (CPM), MAX.3 antigen and CD105. However, MAC within spheroids of highly differentiated papillary RT4 cells failed only the single antigen CD51, whereas MAC expressed the complete maturation-associated phenotype within non-tumorigenic HCV29 spheroids. Interestingly, the suppressive effect of J82 carcinoma cells could only be observed in 3-dimensional but not in monolayer cultures. The J82-MCS induced suppression of CPM and MAX.3 expression was only seen to be operative on infiltrating blood MO: MO first differentiated for 2 days and subsequently co-cultured with J82-MCS showed normal expression of MAX.3 and CPM within the spheroid. Besides the modulation of MAC phenotype, the cytokine response of intraspheroidal MAC was analyzed: upon co-culture MO secreted high IL-1beta and IL-6 but low amounts of TNF-alpha as compared to MAC. This MO typical cytokine pattern remained constant for up to 8 days in culture, again indicating a disturbed MO to MAC maturation within tumor spheroids. In conclusion, a 3-dimensional interaction with tumor cells in vitro results in significant changes in the phenotype and function of the spheroid-associated MO and MAC