Increased levels of laminin in ascitic fluid of patients with ovarian cancer

Byers, Lowell J.; Osborne, Janet; Carson, Linda F.; Carter, Jonathan; Haney, A.F.; Weinberg, J. Brice; Ramakrishnan, Sundaram

doi:10.1016/0304-3835(94)03625-s

Cited by 26 publications

(17 citation statements)

References 11 publications

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“…26 During progression of ovarian serous carcinoma, cells are frequently exfoliated from the ovary surface, consistent with an irregular distribution of a6b4 in tumors and a decrease in a6b4 expression in free-floating ascitic cells. 26 Laminin production and release from established ovarian cancer lines and ascitic cells is also highly increased compared to normal cells, 27 in keeping with the implication of this molecule in tumor cell migration and invasion. 28,29 Studies regarding the absolute levels and pattern of expression of other integrins and cell adhesion molecules are in progress using both monolayer and organotypic cultures of anti-FR intrabody transfectants.…”

Section: Discussionmentioning

confidence: 65%

Reversion of transformed phenotype in ovarian cancer cells by intracellular expression of anti folate receptor antibodies

et al. 2003

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The a-folate receptor (FR) is selectively overexpressed in 90% of nonmucinous ovarian carcinomas, whereas no expression is detectable in normal ovarian surface epithelium (OSE). Indirect evidence suggests that FR expression is associated with tumor progression and affects cell proliferation. To evaluate better the role of FR, we developed an approach based on intracellular expression of single-chain (sc) antibodies (intrabody) to downmodulate membrane expression of FR in ovary cancer cells. IGROV-1 and SKOV3 ovarian carcinoma cell lines were transfected with an anti-FR intrabody. Transfectants and parental cells were tested for FR, integrins and anti-FR intrabody expression by fluorescence-activated cell sorting (FACS), reverse transcription and polymerase chain reaction (RT-PCR) and/or immunoblotting. Cell growth characteristics and adhesion properties were evaluated in liquid, semisolid and organotypic cultures. The anti-FR scFv inhibited FR expression from 60 to 99%. At physiological concentrations of folate, proliferation varied directly as a function of FR expression. FR downmodulation was accompanied by reduced colonyforming ability in soft agar, morphological change of the cells, significant enhanced adhesion to laminin or Matrigel, a twoto three-fold increase in a6b4 integrin expression, and a marked reduction in laminin production. In three-dimensional organotypic cultures, anti-FR intrabody-transfected IGROV1 cells grew as a single-ordered layer, reminiscent of normal OSE growth in vivo. In conclusion, the anti-FR intrabody reverses the transformed phenotype in ovary cancer cells and may provide an efficient means to inhibit selectively the growth of these cells.

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Section: Discussionmentioning

confidence: 65%

Reversion of transformed phenotype in ovarian cancer cells by intracellular expression of anti folate receptor antibodies

et al. 2003

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“…metastasis are secreted abundantly in ascites, fibronectin, lysophosphatidic acid, hyaluran, and vascular endothelial growth factor, making the i.p. milieu favorable for cancer cell growth (11,46). The presence of TG2 in the peritoneal fluid may play a role in remodeling the oncomatrix by cross-linking of ECM proteins.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Peritoneal Ovarian Tumor Dissemination by Tissue Transglutaminase

et al. 2007

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Tissue transglutaminase (TG2) is involved in Ca 2+ -dependent aggregation and polymerization of proteins. We previously reported that TG2 mRNA is up-regulated in epithelial ovarian cancer (EOC) cells compared with normal ovarian epithelium. Here, we show overexpression of the TG2 protein in ovarian cancer cells and tumors and its secretion in ascites fluid and define its role in EOC. By stable knockdown and overexpression, we show that TG2 enhances EOC cell adhesion to fibronectin and directional cell migration. This phenotype is preserved in vivo, where the pattern of tumor dissemination in the peritoneal space is dependent on TG2 expression levels.

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“…The roles of laminins in ovarian cancer development and in tumor metastasis and proliferation in particular have been demonstrated (36,37). In addition, ovarian cancer cells express high levels of ␤ 1 integrin (21-23).…”

Section: Discussionmentioning

confidence: 99%

Caspase-3-dependent Activation of Calcium-independent Phospholipase A2 Enhances Cell Migration in Non-apoptotic Ovarian Cancer Cells

Zhao

Wang

Zhao

et al. 2006

Journal of Biological Chemistry

102

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Calcium-independent phospholipase A 2 (iPLA 2 ) plays a pivotal role in phospholipid remodeling and many other biological processes, including inflammation and cancer development. iPLA 2 can be activated by caspase-3 via a proteolytic process in apoptotic cells. In this study we identify novel signaling and functional loops of iPLA 2 activation leading to migration of non-apoptotic human ovarian cancer cells. The extracellular matrix protein, laminin-10/11, but not collagen I, induces integrin-and caspase-3-dependent cleavage and activation of overexpressed and endogenous iPLA 2 . The truncated iPLA 2 (amino acids 514 -806) generates lysophosphatidic acid and arachidonic acid. Arachidonic acid is important for enhancing cell migration toward laminin-10/11. Lysophosphatidic acid activates Akt that in turn acts in a feedback loop to block the cleavage of poly-(ADP-ribose) polymerase and DNA fragmentation factor as well as prevent apoptosis. By using pharmacological inhibitors, blocking antibodies, and genetic approaches (such as point mutations, dominant negative forms of genes, and siRNAs against specific targets), we show that ␤ 1 , but not ␤ 4 , integrin is involved in iPLA 2 activation and cell migration to laminin-10/ 11. The role of caspase-3 in iPLA 2 activation and cell migration are supported by several lines of evidence. 1) Point mutation of Asp 513 (a cleavage site of caspase-3 in iPLA 2 ) to Ala blocks laminin-10/11-induced cleavage and activation of overexpressed iPLA 2 , whereas mutation of Asp 733 to Ala has no such effect, 2) treatment of inhibitors or a small interfering RNA against caspase-3 results in decreased cell migration toward laminin-10/11, and 3) selective caspase-3 inhibitor blocks cleavage of endogenous iPLA 2 induced by laminin-10/11. Importantly, small interfering RNA-mediated down-regulation of endogenous iPLA 2 expression in ovarian carcinoma HEY cells results in decreased migration toward laminin, suggesting that our findings are pathophysiologically important.

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Increased levels of laminin in ascitic fluid of patients with ovarian cancer

Cited by 26 publications

References 11 publications

Reversion of transformed phenotype in ovarian cancer cells by intracellular expression of anti folate receptor antibodies

Reversion of transformed phenotype in ovarian cancer cells by intracellular expression of anti folate receptor antibodies

Enhanced Peritoneal Ovarian Tumor Dissemination by Tissue Transglutaminase

Caspase-3-dependent Activation of Calcium-independent Phospholipase A2 Enhances Cell Migration in Non-apoptotic Ovarian Cancer Cells

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