cathepsin-g and Adenocarcinoma

In tumor metastasis, multicellular aggregates of tumor cells form and disseminate into the blood or lymph vessels from the tumor mass, following the formation of tumor cell emboli in distant vessels. However, the mechanism by which aggregates form in the tumor mass is unknown. Neutrophils often exist in tumors and are considered to affect tumor development. We observed that neutrophils had the capacity to induce the aggregation of MCF-7 human breast carcinoma cells adhering to culture substrates. When MCF-7 cells were cultured with rat inflammatory neutrophils, the soluble fraction of their lysate, and the conditioned medium of neutrophils stimulated with N-formyl-Met-Leu-Phe plus cytochalasin B, multicellular aggregates formed within 16 h, and tightly aggregated 3-D spheroids formed when the cultures were prolonged. The spheroid-inducing reaction was reversible and energy-dependent. The MCF-7 cells induced to aggregate by the neutrophil extract showed growth potential, although the growth rate of the cells was slightly reduced. The aggregation was dependent on E-cadherin, because the spheroids dispersed into isolated cells on incubation with EGTA or anti-E-cadherin antibody following pipetting. The aggregation-inducing activity in neutrophils was completely inhibited by soybean trypsin-chymotrypsin inhibitor. Moreover, the commercially available human neutrophil elastase and cathepsin G induced the aggregation of MCF-7 cells and formation of spheroids. The proteases secreted by infiltrated neutrophils in tumors are implicated in the dissemination of tumor aggregates from primary tumor sites.

Topics: Adenocarcinoma; Animals; Breast Neoplasms; Cadherins; Cathepsin G; Cathepsins; Cell Adhesion; Female; Humans; Neoplasm Metastasis; Neutrophils; Pancreatic Elastase; Rats; Serine Endopeptidases; Spheroids, Cellular; Tumor Cells, Cultured

Activity and tissue localization of cathepsin G were examined in tumors deriving from 73 patients with non small cell lung cancer. Activity of cathepsin G was highest in adenocarcinoma, lower in planoepitheliale cancer, the lowest in macrocellular cancer. In all histological types of tumors cathepsin G activity in supernatants was lower than in sediments. The enzyme immunohistochemically was localized in neutrophils. There is evident correlation between neutrophil numbers and cathepsin G activity in examined cancer types. Result of our examinations indicate a relationship between cathepsin G activity, grade of tumor differentiation and particular clinical stages of disease.

Topics: Adenocarcinoma; Adult; Aged; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cathepsin G; Cathepsins; Cell Differentiation; Cell Fractionation; Female; Humans; Lung; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Proteins; Neoplasm Staging; Neutrophils; Serine Endopeptidases; Solubility