Summary The immunohistochemical expression of c-kit proto-oncogene product in 57 breast cancer tissues was studied using anti-c-kit proto-oncogene product antibody in comparison with 20 normal breast tissues and 58 benign breast tumours. In normal breast tissues, the c-kit proto-oncogene product was strongly expressed on cell membrane and/or cytoplasm of alveolar and ductal cells. The immunoreactive score (IRS) of c-kit protooncogene product in normal mammary epithelia was 6.22 + 2.11 (mean + s.d.). In benign breast diseases, the ckit proto-oncogene product was detected heterogeneously with a reduced IRS (3.33+2.44). In breast cancer tissues, the expression of the immunoreactive c-kit proto-oncogene product was often deleted and the average IRS was significantly reduced compared to those of normal breast tissues or benign breast disease tissues. Among benign diseases, the average IRS of intraductal papilloma was significantly reduced (1.34+1.70) and the staining intensity and pattern were found to be similar to those seen in breast cancer. The results in this study suggested that the c-kit proto-oncogene product is correlated with the growth control or the differentiation of normal breast epithelium. Also, the loss of the expression of this protein may indicate the change of the signal transduction in relation to malignant transformation in human mammary epithelium.
Summary In this study, the immunohistochemical expression of a new inducible elastase inhibitor, SKALP (skin-derived antileucoproteinase)/elafin, in the tissue of squamous cell carcinoma and uninvolved oesophageal mucosa was studied using a polyclonal rabbit anti-serum against SKALP/elafin. The results were compared with the immunohistochemical staining of proliferating cell nuclear antigen (PCNA) and the TUNEL assay in serial sections. In non-malignant oesophageal mucosa, the expression of SKALP/elafin was localized in the cells of the stratified zone overlying the PCNA-positive basal zone. In oesophageal cancer, the incidence of the expression was significantly related to the degree of the differentiation of the tumour. Characteristically, the expression was almost limited in tumour cell nests that had a clear squamous phenotype. In tumour cell nests, the expression of SKALP/elafin was localized in the cells overlying PCNA-expressing cells and no expression was found in the cells that expressed PCNA; DNA fragmentation was often observed in the same cell layers as those in which SKALP/elafin immunoreactivity was found. This enzyme inhibitor is speculated to be involved in the induction of the cell differentiation and apoptosis of human squamous cell carcinoma cells of the oesophagus.Keywords: SKALP/elafin; oesophageal cancer; immunohistochemistry Squamous cell carcinoma (SCC) is the major histological type of oesophageal cancer in Japan, being one of the most lethal neoplasms of the digestive organs. At present, only limited numbers of patients can be cured by conventional therapy, such as surgical resection, irradiation and chemotherapy, one reason being that oesophageal cancer has an extremely high potential for invasion into the surrounding organs and for metastasis. Several proteases produced by the cancer cell itself have been reported to be associated with cancer invasion and metastasis (Liotta et al, 1980(Liotta et al, , 1986Wooley, 1984;Nakajima et al, 1987;Reich et al, 1988;Basset et al, 1990). Also several kinds of specific inhibitors of such proteases have been shown to inhibit cancer invasion and metastasis (Baker et al, 1990;Cajot et al, 1990;Albini et al, 1991;Declerck et al, 1992;Kennedy, 1994;Kobayashi et al, 1994Kobayashi et al, , 1995. Hence, the protease inhibitors could be considered to possess the potential to be a useful tool for the development of a new therapeutic method against cancer.Recently, a new inducible elastase inhibitor, SKALP (skinderived antileucoproteinase) has been isolated from psoriatic skin (Schalkwijk et al, 1990. SKALP has been shown to be a heat-stable, cationic protein with an apparent molecular weight of 9-11 kDa. DNA of SKALP has been cloned and sequenced (Schalkwijk et al, 1991) and has proved to be identical to elafin, which is a similar epidermal protease inhibitor described by Wiedow et al (1990). The expression of SKALP/elafin has not been found in the cells of normal epidermis but is found in differentiating cells of psoriasis and wound healing (Schalkwijk et...
The immunohistochemical distribution of RON receptor tyrosine kinase in digestive organs of both human fetus and adult, including the esophagus, stomach, duodenum, small intestine, colon, rectum, liver, gallbladder, pancreas, and spleen, was investigated semiquantitively using an affinity-purified rabbit polyclonal antibody. RON was observed to be widely distributed throughout various digestive organs and cell types in humans. The immunoreactivity for RON was observed in the epithelium of the esophagus, small intestine, colon, hepatocytes, Kupffer cells, and splenic macrophages both in the adult and the fetus, suggesting that the MSP/RON signaling pathway possesses the proper biological properties to possibly be involved in morphogenesis or differentiation of cells in these organs and cell types. Several organs differed in immunoreactivity between adult and fetus. No immunoreactive cells were found in the pancreas of adults; however, immunoreactivity was observed in acinar cells and in some of the duct or ductular cells and endocrine cells of the islet of the fetus. Similarly, immunoreactivity was not observed in gastric mucosa except in the intestinal metaplastic cells in adults; however, immunoreactivity was found in the foveolar epithelium of the stomach of the fetus. Although the biological significance of RON in malignancy is unclear, the presence of RON immunoreactivity in the fetus and it lack in the adult may indicate that RON is a oncofetal substance in human pancreas and stomach.
Background. Two pancreatic cancer cell lines, the highly invasive and metastatic cell line PC‐1.0 and the weakly invasive and rarely metastatic cell line PC‐1, were established from a pancreatic ductal carcinoma induced by N‐nitrosobis (2‐oxopropyl) amine in a Syrian golden hamster. Methods. The cancer cell dissociation activity in serum‐free conditioned medium of PC‐1.0 cells was partially purified using a heparin column, a hydroxylapatite column, anion exchange, and gel filtration high‐performance liquid chromatography. Several biologic properties of the partially purified activity were evaluated. Results. Two cell lines exhibited different growth morphologic changes in vitro: the weakly invasive cell line PC‐1 formed islandlike colonies, and the highly invasive cell line PC‐1.0 grew mainly as single cells. The conditioned medium of PC‐1.0 cells induced dissociation of islandlike colonies and morphologic changes of PC‐1 cells to elongated cells, with a high frequency of pseudopodia formation similar to the morphologic findings of PC‐1.0 cells. The dissociation activity did not bind to the heparin column and had an apparent molecular mass of → 400 kDa, as deduced from gel filtration. Several immunoreactive proteinous bands were observed in immunoblotting analysis using a polyclonal blocking antibody. The partially purified activity enhanced cell motility, chemoinvasion, and cell adhesion to plastic plates and fibronectin. Conclusions. Highly invasive and metastatic PC‐1.0 cells produce a soluble proteinous factor, called “dissociation factor” (DF), which induces cell dissociation of weakly invasive and rarely metastatic PC‐1 cells. It seems likely that DF has a role in tumor invasion and metastasis. Cancer 1995;75:1554‐61.
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