We studied the effect of tumoral microenvironments on metastatic phenotypes. Therefore, murine mammary adenocarcinoma cells cultured in vivo in diffusion chambers (DC) were implanted intraperitoneally in BALB/c mice. The behavior of DC-cultured cells was compared with that of cells obtained from tumors growing subcutaneously or intraperitoneally and from primary cultures in vitro of the former. DC-cultured and control cells were inoculated into normal mice to evaluate their tumorigenicity and metastasizing ability. We found that DC-cultured cells were less tumorigenic and metastatic both in spontaneous and in experimental metastasis assays. The host reponse to tumor progression resulted in an early leukocytosis, probably due to the overproduction of a hematopoietic factor by the tumor cells. Finally, it was found that DC-cultured cells produced lower levels of urokinase-type plasmino-gen activator activity, while no differences were found in the metalloproteinase production compared to cells obtained from a tumor growing subcutaneously.
BackgroundComprehensive analyses have recently been performed on many human cancer tissues, leading to the identification of a number of mutated genes but providing no information on the variety of mutations present in each of them. This information is of interest to understand the possible origin of gene mutations that cause tumors.Methodology/Principal FindingsWe have analyzed the sequence heterogeneity of the transcripts of the human HPRT and G6PD single copy genes that are not considered tumor markers. Analyses have been performed on different colon cancers and on the nearby histologically normal tissues of two male patients. Several copies of each cDNA, which were produced by cloning the RT-PCR-amplified fragments of the specific mRNA, have been sequenced. Similar analyses have been performed on blood samples of two ostensibly healthy males as reference controls. The sequence heterogeneity of the HPRT and G6PD genes was also determined on DNA from tumor tissues. The employed analytical approach revealed the presence of low-frequency mutations not detectable by other procedures. The results show that genetic heterogeneity is detectable in HPRT and G6PD transcripts in both tumors and nearby healthy tissues of the two studied colon tumors. Similar frequencies of mutations are observed in patient genomic DNA, indicating that mutations have a somatic origin. HPRT transcripts show genetic heterogeneity also in healthy individuals, in agreement with previous results on human T-cells, while G6PD transcript heterogeneity is a characteristic of the patient tissues. Interestingly, data on TP53 show little, if any, heterogeneity in the same tissues.Conclusions/SignificanceThese findings show that genetic heterogeneity is a peculiarity not only of cancer cells but also of the normal tissue where a tumor arises.
Mouse uterine draining lymph node (UDLN) cells, or soluble factors released by them in both phases of the estrous cycle were examined in the graft‐vs‐host (GVH) assay. The immune response during the estrous phase was significantly decreased as compared with diestrous phase; 24‐hour culture supernatant of UDLN cells was also able to decrease GVH activity mounted in F1 hybrids. This difference in reactivity was not found when peripheral nodes (PN) or spleen cells were tested. These results show that in physiological conditions it is possible to detect an hormonal influence on T lymphocyte function and would suggest that a nonspecific immunosuppression would appear even during the estrous phase.
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