asialo-gm1-ganglioside and Precancerous-Conditions

The purpose of this review was to summarize observations on the type and function of inflammatory infiltrates of mouse mammary tumors and to speculate on the underlying mechanisms and the significance of infiltrates to mammary tumor biology. Although the major conclusion is that much more work is needed, certain themes seem to be emerging. The number of infiltrating cells can be very high but is unrelated to biological behavior of the tumors. What seems to be important is the relative contributions of inflammatory cell subsets. In the case of T-cell subsets and NK cells, the infiltrates from tumors of long-term cell lines so far seem uninformative. The general characteristics are similar to those of infiltrates from rapidly proliferating, normal mammary tissues. These characteristics do not correlate with diverse biological behavior or malignant potential. A more informative model appears to be one in which the development of tumors from preneoplastic tissue can be observed. Here our attention is currently focused on NK cells. By contrast, the correlation between activated TAM and metastatic behavior suggests that our transplantable MMT lines may be biologically relevant in the study of infiltrating macrophages. We are especially interested in the role of TAM in the generation of tumor cell variability. Overall, our data indicate that the host infiltrate is another manifestation of both inter- and intra-tumor heterogeneity and, as such, is not simply a response to, but, rather, a part of the tumor ecosystem. Unraveling the cellular and molecular mechanisms that govern the inflammatory cell component of tumors should provide insight into the types of cellular interactions that result in tumor development and progression.

Topics: Animals; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; Cell Adhesion; Cell Movement; Chemotaxis, Leukocyte; G(M1) Ganglioside; Glycosphingolipids; Immunity, Cellular; Immunity, Innate; Inflammation; Killer Cells, Natural; Lymphocyte Activation; Macrophages; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Precancerous Conditions; T-Lymphocytes

Anti-asialo GM1 serum (AGM1) reduces natural killer (NK) activity in vitro and in vivo. We investigated the effect of ingestion of sugar beet fiber (SBF) on 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) and whether the effect was maintained under NK-reducing conditions by AGM1 injection. The ingestion of SBF decreased the number of ACF in the colorectum at 4 weeks after treatment with DMH. Dietary SBF had a suppressive effect on the formation of ACF regardless of the administration of AGM1. These results suggest that the suppressive effect created by the ingestion of SBF may overwhelm the effect of AGM1 treatment on ACF formation.

Topics: Animals; Chenopodiaceae; Colon; Colonic Neoplasms; Colonic Polyps; Dietary Fiber; G(M1) Ganglioside; Intestinal Mucosa; Male; Organ Size; Precancerous Conditions; Rats; Rats, Wistar; Spleen

We investigated the influence of the administration of anti-asialo GM1 antibody on aberrant crypt foci (ACF) formation induced by a single injection of 1,2-dimethylhydrazine (DMH). At four weeks after the injection of DMH (20 mg/kg body weight), the number of ACF and aberrant crypts were counted. Most ACF appeared in the distal large bowel, accounting for approximately 60% of the total ACF in both groups. Rats administered anti-asialo GM1 had significantly more ACF in the distal colon, the rectum and the total large bowel as compared to control rats. A similar tendency was observed for the number of aberrant crypts. The increased number of ACF resulting from the administration of anti-asialo GM1 was not accompanied by the enlargement of ACF size in every part of the colon. This study demonstrated that the administration of anti-asialo GM1 at the initiation stage leads to an increase in ACF as well as aberrant crypts in the distal colon, rectum and total large bowel probably via the suppression of natural killer cells.

Topics: 1,2-Dimethylhydrazine; Animals; Carcinogens; Cocarcinogenesis; Colonic Neoplasms; Dimethylhydrazines; G(M1) Ganglioside; Immune Sera; Killer Cells, Natural; Precancerous Conditions; Rats; Rats, Wistar

Tissue infiltrating lymphocytes isolated from the preneoplastic mouse mammary hyperneoplastic alveolar nodule (HAN) tissue line C4 express high levels of natural killer (NK) activity, which gradually wanes as spontaneous tumors develop (W. Z. Wei and G. Heppner. Br. J. Cancer, 55: 589-594, 1987). Experiments were performed to test whether modulation of NK cell activity would be associated with altered progression of HAN to tumor. Administration of polyinosinic-polycytidylic acid, which activates NK activity but does not directly affect mammary epithelial cell growth, to HAN-bearing mice enhanced tumor progression, as measured by a decrease in the latency period and increase in the incidence of mammary adenocarcinomas developing in the HAN implants. Antiasialo GM1, which reduces NK activity, reduced tumor progression. The net effect of indomethacin, which may inhibit mammary epithelial cell growth but enhances NK cell function, was to prolong the latency period of tumor development. However, this effect was reversed by interleukin 2, which activates NK cells. These findings suggest that NK activity may provide positive signals for progression of preneoplastic mammary lesions to frank neoplasia.

Topics: Animals; Female; G(M1) Ganglioside; Glycosphingolipids; Indomethacin; Interleukin-2; Killer Cells, Natural; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Poly I-C; Precancerous Conditions