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Tumor cell adhesion to frozen lymph node sections--an in vitro correlate of lymphatic metastasis.

Two variant sublines of the murine 3LL carcinoma with divergent potentials for lymphatic metastasis were used to assess the relationship between tumor cell potential for lymphatic metastasis and its ability to adhere specifically to lymphatic tissue. Using fresh cryostat sections of lymph nodes and spleens, it was found that tumor cell adhesion to the lymphatic tissue but not to control sections of the brain correlated well with their ability to metastasize lymphatically. On the other hand, there was no correlation between tumor cell attachment to isolated lymphocytes in vitro and their potential for lymphatic metastasis. When tumor cells were pretreated enzymatically or with the metabolic inhibitor tunicamycin with the aim of modulating cell surface carbohydrates, adhesion to the lymph node sections could be significantly reduced, implicating cell surface glycoproteins and in particular galactosyl groups in the binding. The results suggest that tumor cell attachment to lymph node cryostat sections could provide a useful tool in the study of host-tumor interactions in lymphatic metastasis.

Animals

[Hemorheological study on the process of tumor invasion and lymphatic metastasis].

Mouse transplantable hepatoma (H22) was used as an experimental model for lymphatic metastasis. The tumor cells were transplanted subcutaneously into right footpads of inbred 615-strain mice. The hemorheological changes during invasion and lymphatic metastasis in mice were observed. The results of histological examination showed that tumor invasion was divided into early, middle and late invasive stages, and the metastasis was divided into early, middle, late and final metastasis periods. Tumor invasion began 3 days after tumor transplantation, and the late stage of invasion was found at 9 days. Metastasis began 6 days after transplantation; at 19 days metastasis to lymph nodes in the right side reached grade IV. Metastasis to lymph nodes in the left side appeared 14 days after tumor transplantation. In the early and middle invasive stages only plasma viscosity increased significantly, while other hemorheological values were unchanged. The blood viscosity and aggregation of red blood cells decreased significantly after the metastatic late stage. The hematocrit of red blood cells began to decrease in the final stage of metastasis, and in the meantime, the rigidity of red blood cells began to increase, while plasma viscosity showed no changes after the late metastatic stage. The results and mechanism of hemorheological changes are discussed.

Animals

Studies on lymphatic metastasis. I. Primary immunoregulatory role of regional lymph nodes in the establishment of lymphatic metastases.

The growth of syngeneic ascites MM48 tumor cells implanted in a hind footpad of a C3H/He mouse slowed at 10-12 days after tumor implantation. At that time, no killer activity was detected in all lymphoid organs examined, including regional lymph node. However, positive immunoregulatory activity, i.e., killer-augmenting activity, which was assessed by cytotoxicity assay with tumor-specific immune cytotoxic T-cells, was detected primarily in the regional lymph node. In contrast, local preimmunization with larger doses of irradiated tumor cells enhanced growth of subsequently challenged tumor and lymphatic metastasis. In the regional node of preimmunized tumor bearer, negative immunoregulatory activity, i.e., killer-suppressing activity, was induced. Both immunoregulatory activities were tumor specific and resided in Lyt-1+ T-cells. Tumor-specific immunoregulatory activity seemed to be related to tumor dose used for challenge, whether positive or negative immunoregulatory activity was induced. Lymphatic metastases examined by bioassay and histologic examination were evaluated with reference to immunoregulatory activity that appeared in the regional lymph node during tumor development. The incidence of tumor detection in the node by bioassay was decreased when killer-augmenting activity was present there. Proliferation of metastatic tumor cells judged by microscopic observation was in parallel with suppressor activity generated in the node.

Animals

[Lymphatic metastasis of breast cancer and selection of operation].

Studies of 169 cases of breast carcinoma showed that lymphatic metastasis was closely related to biological behavior of the cancer. Modified radical operation or modified extended radical operation were performed in cases of TNM stage I and II by pre- and intraoperative estimation of the tumor less than or about 5 cm in diameter, limited within mammary gland, and of expansion type. Histological typing and grading, degree of infiltration, condition of ER and lymphatic metastasis were used to plan postoperative adjuvant therapy. The importance of investigation of ER status of the lesions lies in proper arrangement of combined therapy and prediction of prognosis.

Adult

Tumor cell adhesion to frozen lymph node sections--a correlate of lymphatic metastasis in breast carcinoma models of human and rat origin.

The role of tumor cell adhesion in lymphatic metastasis of breast cancer was investigated in vitro using a rat mammary carcinoma model of four cell lines with different metastatic phenotypes, two human breast cancer cell lines, and cryostast sections of normal rat or human lymph nodes, respectively. A positive correlation was found between the adhesion levels obtained with three metastatic rat mammary cell lines (TMT-081 greater than MT-100M & TMT-50) and a non-metastatic line MT-W9B, the latter being 3-4 fold less adhesive to the lymph node sections than the metastatic tumors. This selective adhesion was specific, as it was not found with cryostat sections of rat liver and brain. Enzyme assays indicated that cell surface glycoproteins bearing terminal beta-galactoside residues were involved in the adhesion of the rat tumors. Adhesion of the human breast carcinoma cells Hs578T to sections of human lymph nodes was significantly higher than that of the normal breast epithelial cell line Hs578Bst, and comparable to adhesion of a second breast carcinoma line, MCF-7. Moreover, Hs578T cells isolated from regional lymph nodes of tumor-bearing nude mice were significantly more adhesive to human lymph node sections than the parental line. Adhesion of both human and rat tumors could be partially blocked by the addition of the synthetic peptide GRGDSPK and by antibodies directed to the beta 1 chain of integrin, suggesting that an integrin receptor may played a role in the adhesion. The results suggest that tumor cell adhesion to cryostat sections of lymph nodes is a correlate of the malignant phenotype in mammary tumors of diverse origins, and could be used to delineate the adhesion factors mediating lymphatic metastasis.

Animals

Lymphatic metastasis of tumour; persistent transport of cells.

A model of lymphatic metastasis established by injecting Walker rat carcinoma cells into the rat footpad was used to study the output of tumour cells from the footpad. The lymphatic efferent from the footpad was cannulated in a group of rats with advanced neoplasm; it was shown that the output of tumour cells was continuous over periods up to 90 min and ranged from 10(2)-10(5) cells/min.

Animals

Pathology of malignant tumors of the nose and throat and their relationship to lymphatic metastasis.

One hundred cases of malignant tumors of the larynx, pharynx, oral cavity, nose and paranasal sinuses were studied. The hypopharynx was the most frequent site and the most common type of tumor was squamous cell carcinoma. Lymph nodes were palpable in 59% of cases, of which 72.8% showed histological evidence of metastasis. The highest incidence of metastasis was found in nasopharyngeal growths and the lowest in the nose and the sinuses. In laryngeal tumors the site of the tumor was the most important factor influencing regional lymphatic metastasis. The grade of the tumor influenced the lymph node metastasis in the regions of the hypopharynx, tonsil and base of tongue. At other sites the differentiation of the tumor did not seem to have any correlation with the incidence of metastasis.

Adult

Lymphatic metastasis with childhood rhabdomyosarcoma.

Clinico-pathologic reviews of series of children with rhabdomyosarcoma have yielded conflicting information regarding frequency of lymphatic spread of this disease. The 264 eligible entries in the Intergroup Rhabdomyosarcoma Study (from November 1972 to September 1975) have been categorized by a prospective staging system and pre-treatment characteristics and pathologic findings reviewed. Data accumulated thus far have revealed a higher than expected incidence of lymphatic metastases from extremity (17%) and genito-urinary sites (19%) with a somewhat lower incidence from the orbit (0%), the head and neck region (3%), and trunk (10%). These differences in regard to lymphatic metastases were found to have no relationship to age, sex, tumor size, or histologic type when these factors were simultaneously examined.

Adolescent