The morphological study was aimed at determining the role of fibrillar organization of the collagen-containing connective tissue of prostate cancer at the stage of neoplastic proliferation, including ...metastatic spreading into bone tissue. The histological material of 55 patients with prostate cancer, Gleason six to nine malignancy score, without neoplastic proliferation and with metastases into bones, was used. The architectural specificities of collagen-containing connective tissue of neoplasms were determined using Van Gieson’s method. It was found that the remodeling of collagen-containing connective tissue around the epithelial tumor structures with aggressive prostate cancer (Gleason score of eight to nine) resulted in the increase in the percentage of extended and flattened fibrils as compared to curved fibrils; the adjacent and surrounding stroma was notable for the enlarged total area of collagen-containing fibrils, manifestations of desmoplasia, compactization of the location, widening, flattening, and extending. The data obtained demonstrate that the remodeling of collagen-containing connective tissue components of prostate cancer conditions unrestricted migration and invasion of tumor cells, including those expressing the proteins involved in bone tissue remodeling.
A piece of gelatin sponge was inoculated submesothelially in the abdominal wall of female Donryu rats, and 1, 2, 4, 7, 14, or 21 days later, 1 × 105 cells of ascites hepatoma AH39 were ...intraperitoneally transplanted. Tumor cells were detected in the area of gelatin sponge inoculation in each group 2 to 5 days after the transplantation. Generally, the number of rats in which tumor cells were detected was larger in those transplanted with tumor cells within a short period after the gelatin sponge inoculation. Changes in the area of gelatin sponge inoculation and nontreated area in the rats which received intraperitoneal transplantation of the tumor cells on the 1st day after gelatin sponge inoculation were studied. Tumor cells were detected in the area of gelatin sponge inoculation as early as 2 days after the tumor transplantation, whereas they were detected on the 14th day in nontreated areas. Tumor detection was preceded by inflammatory reaction in both cases.
It has now been well documented that urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play a central role of fibrinolysis at cell surfaces. Further, the importance of this finding ...resides in various cellular regulation of fibrinolysis mediated by cell surface bound inhibitors and other fibrinolytic proteases. Other than those, members of a family of matrix metalloproteinases (MMP) either tightly or loosely bound to cell membranes are also intriguing in the efficient destraction of a surrounding extracellular matrix (ECM) when invasive tumor cells are spreading or tissues are remodeling. Plasminogen activators activate plasminogen as well as some members of latent MMPs. Thus, plasminogen activators and MMPs are thought to be functionally crossoverd at cell surfaces. Those local membrane structures such as adhesion plaque and invadopodia as well may be important biological architectures, where both the receptor, binding sites for plasminogen and other proteolytic enzymes are localized. The former is functioning not only for cell adhesion, but for cellular locomotion, being able to degrade ECM via the activation of membrane bound plasminogen. The latter appears to be organized when invasive tumor cell moves across pores of an ECM-coated invasion chamber by breaching out the proteins. Therefore, both are thought to be active parts of the cellular membrane (domains) being able to interact locally with an ECM area composed of a suprastructure of networks of various monomer types of glycoproteins, such as collagen type IV, proteoglycans and laminin. Here, I briefly describe the background of uPA/uPAR system at the level of cell and molecular biology and further hypothesize that interactions of the two structural domains are also essentially functional motifs; a driving force of the local hydorlysis of ECM and importance of uPA/uPAR dependent locomotion for invasive spread of tumor cell across basement membrane.
Neutrophil gelatinase-associated lipocalin (NGAL) is a novel member of the lipocalin family and may be a new human oncogene product, but function of NGAL is not clear in the cancer. It was recently ...found that NGAL was overexpressed in the progression of malignant transformation from human immortalized esophageal epithelial cell line SHEE to esophageal carcinoma cell line SHEEC. This indicated that cell line SHEEC was a good model for exploring functions of NGAL in the carcinogenesis. The effects of blocking transcription of NGAL gene on invasion, division and proliferation of SHEEC cells were studied by antisense blocking RNA technique and tumor formation in nude mice. The results showed that the antisense blocking of transcription of NGAL gene not only decreased effectively the activity of MMP-9 and MMP-2 secreted by SHEEC cells, but suppressed significantly also the invasion of these cells in nude mice. However, the telomere length, the content of the cellular topoisomerase II-alpha and cellular proliferati
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