Invasion & Metastasis 

About: Invasion & Metastasis is an academic journal. The journal publishes majorly in the area(s): Metastasis & Cell culture. It has an ISSN identifier of 0251-1789. Over the lifetime, 480 publications have been published receiving 13436 citations. The journal is also known as: military invasion.

Expression of heparanase by platelets and circulating cells of the immune system: possible involvement in diapedesis and extravasation.

Abstract: Interaction of T and B lymphocytes, platelets, granulocytes, macrophages and mast cells with the subendothelial extracellular matrix (ECM) is associated with degradation of heparan sulfate (HS) by a specific endoglycosidase (heparanase) activity The enzyme is released from intracellular compartments (ie, lysosomes, specific granules) in response to various activation signals (ie, thrombin, calcium ionophore, immune complexes, antigens, mitogens), suggesting its regulated involvement in inflammation and cellular immunity In contrast, various tumor cells appear to express and secrete heparanase in a constitutive manner, in correlation with their metastatic potential Heparanase enzymes produced by different cell types may exhibit different molecular properties and substrate cleavage specificities The platelet enzyme appears also in a latent form It can be activated by tumor cells and thereby facilitate their extravasation in the process of metastasis Degradation of ECM-HS by all cell types was facilitated by a proteolytic activity residing in the ECM and/or expressed by the invading cells This proteolytic activity produced a more accessible substrate for the heparanase enzymes Heparanase-inhibiting, nonanticoagulant species of heparin markedly reduced the incidence of lung metastasis in experimental animals These species of heparin also significantly impaired the traffic of T lymphocytes and suppressed cellular immune reactivity and experimental autoimmune diseases Heparanase activity expressed by intact cells (ie, platelets, mast cells, neutrophils, lymphoma cells) was found to release active HS-bound basic fibroblast growth factor from ECM and basement membranes Heparanase may thus elicit an indirect neovascular response in processes such as wound repair, inflammation and tumor development The significant anticancerous effect of heparanase-inhibiting molecules may therefore be attributed to their potential inhibition of both tumor invasion and angiogenesis Both normal leukocytic cells and metastatic tumor cells can enter the bloodstream, travel to distant sites and extravasate to the parenchyma at these sites We suggest that heparanase is utilized for this purpose by both types of cells Other functions (ie, enzyme activities, adhesive interactions, chemotactic and proliferative responses) of metastatic tumor cells seem to mimic the equivalent functions of leukocytes as they migrate across blood vessels to gain access to sites of inflammation

A new in vitro assay for quantitating tumor cell invasion.

Abstract: The attachment to and penetration of basement membranes by tumor cells is required to complete the metastatic cascade which culminates in the establishment of secondary tumor foci. Therefore, basement membranes are critical barriers to the passage of disseminating tumor cells. We have developed a simple, in vitro model using matrigel-coated transwell chambers (Costar) for use in a tumor cell invasion assay. Two variants of the K1735 UV-induced murine melanoma cell line were assayed for their invasive capabilities and compared with their ability to colonize the lung in an experimental metastasis assay. The K1735-M2 cells, which are highly metastatic in vivo, invaded through basement membrane matrigel at a significantly higher rate than the low metastatic cells, K1735-16, in a 72-hour assay. As a negative control, normal murine fibroblasts were incapable of penetrating the barrier. Tumor cell invasion in vitro correlated with lung colonization in vivo. Therefore, this model may provide a valuable tool to study the mechanisms involved in the pathogenesis of tumor cell invasion during hematogenous dissemination.

Characterization of metastatic heterogeneity among subpopulations of a single mouse mammary tumor: heterogeneity in phenotypic stability.

Abstract: The frequency of metastasis formed by tumor cells injected into lateral tail veins, mammary fatpads, or the subcutis are described for eight subpopulations of a single, spontaneously arising BALB/cfC3H mouse mammary tumor. These subpopulations display a spectrum of metastatic behavior from all three injection sites. The proportion of animals with metastases does not depend upon the site of primary tumor growth (i.e., mammary fatpad versus subcutis). One subpopulation can grow as lung nodules after intravenous injection but is only poorly metastatic from subcutaneous or fatpad implants. Heterogeneity among the subpopulations in the stability of the metastatic phenotype is evident. Although most of the subpopulations and their clones remained stable for periods of 2-5 years, one subpopulation rapidly lost metastatic ability within 3 months and another gradually became more metastatic over 2 years.

Metalloproteinases in tumor progression: the contribution of MMP-9.

Abstract: Many enzymes capable of proteolytic degradation of extracellular matrix and basement membranes have been implicated in tumor progression, including the matrix metalloproteinases, cathepsins, plasminogen activators, and heparanase. Matrix metalloproteinases, a family of zinc-dependent proteases, participate in several steps in tumor progression, including invasion, metastasis, and angiogenesis. In this review, we will give a brief overview of this protease family, and we will review in vitro and in vivo evidence implicating a particular metalloproteinase, the 92-kD type IV collagenase/gelatinase (MMP-9 or gelatinase B), as well as other metalloproteinases, in cancer progression. Finally, using recent studies from our laboratory, we will demonstrate the importance of both tumor cell and host stromal cell production of MMP-9 in tumor progression.

Effect of phorbol ester and cytokines on matrix metalloproteinase and tissue inhibitor of metalloproteinase expression in tumor and normal cell lines.

Abstract: The effect of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and the cytokines interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) on matrix metalloproteinases (MMP) and metalloproteinase inhibitors was studied in a variety of human cell lines. Expression of the mammalian collagenase (MMP-1), 72-kD gelatinase/type IV collagenase (MMP-2), stromelysin (MMP-3), 92-kD gelatinase/type IV collagenase (MMP-9), and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) was assessed by zymography and Northern blot analysis. MMP-2 and TIMP-2 activities were refractory to TPA, IL-1 and TNF-alpha treatment in most of the cell lines. In contrast, MMP-3, MMP-9 and TIMP-1 activities were markedly stimulated by TPA in most of the tumor cell lines and human umbilical vein endothelial cells (HUVEC), whereas the fibroblast lines were minimally stimulated or unresponsive to TPA. The MMP-3, MMP-9 and TIMP-1 stimulation in response to IL-1 and TNF-alpha treatment was detected in some of the tumor cell lines and HUVEC. The increase in activity was less marked than in TPA. A breast carcinoma cell line, MDA-MB-231, which did not express MMP-2, had high expression of MMP-3 and MMP-9 which were unaffected by TPA and cytokine treatment. Northern blot analysis of MMP and TIMP mRNA expression reflected the zymogram findings for most of the cell lines. TPA-mediated stimulation of MMP-1 was similar to that of MMP-3 and MMP-9. Exceptions were the fibroblast cell lines which showed either a much more marked mRNA response of MMP-9 to TPA than observed at protein level, or a high constitutive MMP-9 mRNA when MMP-9 activity was not detectable by zymography. TPA-mediated stimulation of MMP-9 and TIMP-1 activity was blocked by staurosporine, an inhibitor of protein kinase C (PKC). A non-PKC-activating phorbol ester, 4 alpha-phorbol-12,13-didecanoate, did not stimulate MMP-9 and TIMP-1 activity. TPA treatment caused the increased expression of c-fos containing AP-1-specific binding activity in selected tumor cell lines. This activity was maximal at 6 h. An association was observed between AP-1 binding activity and increased expression of MMP-1, MMP-3 and MMP-9, which possess TPA-responsive elements (TRE). TPA-sensitive MMPs and TIMP-1 were variably stimulated by biologically relevant cytokines, such as IL-1 and TNF-alpha.(ABSTRACT TRUNCATED AT 400 WORDS)