Biomedical subjects

M Koutsilieris

Publications and source records attributed to M Koutsilieris.

80 records · Page 5Linked to original sources

PubMedDate not supplied

Osteoblastic metastasis in advanced prostate cancer.

Metastatic prostate cancer is unique in its ability to induce the osteoblastic reaction in skeleton. This phenomenon is probably the result of complex paracrine/autocrine cell interaction between prostate cancer cells and bone cells at the metastatic sites. Recently the use of various in vivo and in vitro systems made possible the confirmation of certain cellular interactions that may participate in this process. The role of IGFs/GFBPs, urokinase-type plasminogen activator (uPA), as well as of TGF beta 1 and glucocorticoids is discussed in this review.

Adenocarcinoma↗

PubMedDate not supplied

Three-dimensional type I collagen gel system containing MG-63 osteoblasts-like cells as a model for studying local bone reaction caused by metastatic cancer cells.

We inoculated the KLE human endometrial cancer, MCF-7 and ZR-75 human breast cancer, and PC-3 human prostate cancer cells into three-dimensional type I collagen gel system that contained uniformy dispersed MG-63 osteoblast-like cells. Then, we analyzed the morphological evidence of osteoblasts reaction, local invasion around the inoculated cancer cells and expression of the cathepsin D and urokinase-type plasminogen activator (uPA) around the sites of inoculation using immunocytochemistry. The prostate cancer cells produced morphological evidence of blastic reaction presented as an increased number of MG-63 osteoblasts and increase density of type I collagen around the sites of inoculation with PC-3 cells. The inoculated MCF-7 and ZR-75 cells decreased the density of type I collagen and number of osteoblasts and invaded the collagen gel around the sites of inoculation. The KLE endometrial cancer cells and cell-free media produced no reaction at the inoculation sites suggestive of cancer cell-specific interactions with osteoblasts in this system. The expression of uPA was remarkably higher at the inoculation sites of PC-3 cells as compared with those of the other cancer cells. Cathepsin D expression was higher at the sites of inoculation with KLE, MCF-7 and PC-3 cancer cells. MG-63 osteoblasts contained relatively low expression of uPA and cathepsin D. We conclude that this collagen gel system is a useful model for studying the morphological evidence of local invasion and osteoblasts reaction produced in response to local growth of metastatic cancer cell in vitro.

Bone Neoplasms↗

PubMedDate not supplied

Association of protease activity against IGFBP-3 with peritoneal fluid mitogens: possible implications for the ectopic growth of endometrial cells in women with endometriosis.

BACKGROUND: Recent data indicate the implication of an IGF/IGFBP/protease system in the development of ectopic implants of endometrium (endometriosis) in the pelvic cavity. MATERIAL AND METHODS: We characterized mitogens and protease(s) against IGFBP-3 in the peritoneal fluid of women with or without endometriosis using preparative isoelectric focusing (IEC) Proteineous fractions were tested for a) mitogenic activity on NIH/3T3 cells and KLE endometrial-like cells, b) proteinolytic activity against radiolabeled IGFBP-3, and c) protein analysis using SDS-PAGE. RESULTS: A significant increase in the DNA content of cultured cell lines was found in PF fractions having slightly acidic or alkaline pH and containing mainly proteins with molecular weights between 50 and 25 kD. These fractions were also found to cleave IGFBP-3 into 25, 18 and 14 kD fragments. Both activities were present in the PF of subjects with or without endometriosis. CONCLUSION: The preparative isoelectric focusing system would be an advantageous approach to investigate the possible implication of the PF proteases with IGFBP-3 limited proteolysis generating PF mitogen(s) which possibly participate in the pathophysiology of endometriosis.

3T3 Cells↗

PubMedDate not supplied

Growth factors mediate glucocorticoid receptor function and dexamethasone-induced regression of osteoblastic lesions in hormone refractory prostate cancer.

We investigated the ability of important regulators of osteoblast function, such as insulin-like growth factor I (IGF-I), transforming growth factor beta 1 (TGF beta 1), and urokinase-type plasminogen activator (uPA) to act as mediators in cell-cell interactions between osteoblast-like cells and metastatic prostate cancer cells, in vitro. In addition, we assessed whether these growth substances can (a) mediate glucocorticoid receptor (GR) function and (b) be implicated in dexamethasone-induced regression of osteoblastic tumors. Exogenous IGF-I, rat/human uPA, and PA-III (rat)/PC-3 (human) prostate cancer cells conditioned media (CM) stimulated the proliferation of rat (UMR 106 cells) and human (MG-63 cells) osteosarcoma cells. This mitogenic activity was completely neutralized by anti-IGF-I specific antibody. In addition, dexamethasone decreased cell growth, up regulated TGF beta 1 mRNA, and down regulated uPA mRNA expression in prostate cancer cells. Furthermore, it inhibited cell growth by activating latent-TGF beta 1 in osteoblast-like cells. In addition, dexamethasone down regulated the expression of IGF-I mRNA in osteoblast-like cells. Therefore, it is conceivable that uPA, TGF beta 1 and IGF-I mediate at least in part cell-cell interactions and GR function in osteoblastic metastases. Conceivably, regression of the osteoblastic tumors produced by high-dose dexamethasone treatment in hormone-refractory prostate cancer patients is been mediated by differential regulation of growth factors, locally.

Animals↗

PubMedDate not supplied

Pulmonary metastases in metastatic prostate cancer: host tissue-tumor cell interactions and response to hormone therapy.

Stage D2 prostate cancer patients with pulmonary metastases and absence of detectable metastases in bones are quite rare and almost always show accompanying favorable and long-term clinical response to hormone therapy. We present a case of a patient with pulmonary metastases caused by prostate cancer who experienced 13-year complete clinical response to GnRH analogues and we discuss the possible implications of host tissue-metastatic cancer cell interactions in pulmonary metastases and clinical response to hormone depletion therapy.

Adenocarcinoma↗

PubMedDate not supplied

Mast cell-tumor cell interactions: for or against tumour growth and metastasis?

This review comes up with the possible association between mast cells and tumour progression and summarizes some of the most recent data on the subject. The accumulation of mast cells around tumour areas is a very old observation. However, the functional significance of such phenomenon is a subject of controversy because of contradictory experimental data. In this review, two hypotheses are suggested. The first, refers on the possibility that the accumulation of mast cells is part of a general immunological host-defense reaction since, mast cells have been shown to be cytotoxic for some tumours (especially those sensitive to tumor necrosis factor-alpha). However, if such hypothesis is correct, one should explain why in most clinical and experimental cases, tumours continue to progress although the high incidence of such immune's system cells. We are therefore brought to consider a second possibility, in which, mast cells products could promote tumoural growth and metastasis. In fact, it is well documented that heparin, combined to a range of heparin-binding factors such as bFGF or TGF beta is able to promote neovascularisation, and that mast cell proteases cause cell structural alterations and loss of the extracellular matrix integrity. The role of histamine secreted by mast cells is less clear. There is indeed controversial experimental data referring to histamine's content within tumoural tissues and to histamine's proper effect on tumour expansion. Finally, this review discuss the mechanisms resulting to mast cell accumulation around tumours and more particularly the contribution of tumoural cells.

Animals↗

PubMedDate not supplied

Stromal fibroblasts are required for PC-3 human prostate cancer cells to produce capillary-like formation of endothelial cells in a three-dimensional co-culture system.

The outcome of patients with prostate cancer is largely dependent on the ability of the primary tumor for local invasion, angiogenesis and metastasis. To better understand the cell-cell interactions that participate in prostate cancer neovascularization, we have developed a novel three-dimensional co-culture system. Capillary-like structures were induced in fibrin gel in which collagen gels containing fibroblasts and/or PC-3 human prostate adenocarcinoma cells were sandwiched together. In the presence of collagen-embedded fibroblasts, angiogenesis apparently occurred, while endothelial cells did not survive when only PC-3 cells were embedded in collagen. In contrast, when PC-3 cells were combined with fibroblasts in collagen gel an enhanced formation of capillary-like structure formation was noted, particularly using FGF-2-supplemented medium. In addition, we observed morphological evidence of PC-3 cells and fibroblast invasion into fibrin using this system. Therefore, we conclude that fibroblasts apparently play an important role in angiogenesis and tumor invasion. Furthermore, this novel three-dimensional co-culture is apparently a promising model for studying de novo angiogenesis and tumor invasion in vitro.

Adenocarcinoma↗

PubMedDate not supplied

Osteoblast-derived growth factors enhance adriamycin-cytostasis of MCF-7 human breast cancer cells.

Bone only metastasis in patients with estrogen receptor (ER) positive breast cancer reported to have favorable response to chemotherapy, favorable prognosis, and an "indolent" course. Therefore, we assessed the ability of MG-63 osteoblast-like human osteosarcoma cells (MG-63 cells) and MG-63 conditioned media (CM) to influence adriamycin-cytotoxicity of ER-positive MCF-7 human breast cancer cells. Estradiol (E2; 100 nM) increased the distribution at S and G2/M phases in the cell cycle and stimulated the growth of MCF-7 cells. Adriamycin (100 nM) inhibited the growth and arrested the MCF-7 cells supplemented with or without 100 nM of estradiol [(-E2) and (+E2) MCF-7 cultures] at G2/M phase in the cell cycle. In addition, adriamycin (100 nM) increased the distribution at G1/G0 phase in the cell cycle of (+E2) MCF-7 cultures. Adriamycin (100 nM and 10 microM) did not induce apoptosis of MCF-7 cells as assessed by flow cytometry and analysis of DNA fragmentation on simple agarose gel. Exogenous insulin-like growth factor I (IGF I) stimulated while transforming growth factor beta 1 (TGF beta 1) and MG-63 CM inhibited the growth of MCF-7 cells. Furthermore, MG-63 CM and TGF beta 1 enhanced while exogenous IGF I reversed adriamycin (100 nM)-cytostasis of MCF-7 cells. These data suggested that osteoblastic CM contained growth factors, such as TGF beta 1 capable of enhancing adriamycin-cytostasis, in vitro. Conceivably, these osteoblast-derived "enhancers" of chemotherapy-cytostasis can explain the favorable prognosis and "indolent" course of ER-positive breast cancer patients with bone only metastasis.

Antineoplastic Agents↗