Tumor cell adhesion to the extracellular matrix and signal transduction mechanisms implicated in tumor cell motility, invasion and metastasis

1992 ◽  
Vol 11 (1) ◽  
pp. 31-44 ◽  
Author(s):  
Bruce R. Lester ◽  
James B. McCarthy
Keyword(s):  
Signal Transduction ◽  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Tumor Cell ◽  
Cell Motility ◽  
Invasion And Metastasis ◽  
Tumor Cell Adhesion ◽  
Tumor Cell Motility ◽  
Transduction Mechanisms

ROLE OF PLATELET GLYCOPROTEINS lb AND llb/llla IN TUMOR CELL INDUCED PLATELET AGGREGATION AND TUMOR CELL ADHESION TO EXTRACELLULAR MATRIX. I. Grossi

1987 ◽  
Author(s):  
L Grossi ◽  
K V Honn ◽  
B F Sloane ◽  
J Thomopson ◽  
D Ohannesian ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Platelet Aggregation ◽  
Tumor Cell ◽  
Platelet Adhesion ◽  
Eicosatetraenoic Acid ◽  
Platelet Glycoprotein ◽  
Dependent Manner ◽  
Tumor Cell Adhesion ◽  
Dose Dependent

Platelet glycoproteins are known to play a role in platelet platelet interactions, platelet activation, and platelet adhesion to extracellular matrix (ECM). Monoclonal antibody to human platelet glycoprotein lb (mAblb) and polyclonal antibodies to the llb/llla complex (pAbllb/llla) were used to evaluate the involvement of these glycoproteins in tumor cellinduced platelet aggregation (TCIPA and tumor cell adhesion to the ECM. We have demonstrated that human cervical carcinoma (MS5I7), human colon carcinoma (Clone A), and rat Walker 256 carcinosarcoma (W256) cells induce aggregation of homologous platelets via thrombin generation. MAblb and pAbllb/llla were shown to inhibit TCIPA by MS517, Clone A, and W256 in a dose dependent manner. MAblb was also shown to inhibit platelet thromboxane B2 production in response to tumor cells in a dose dependent manner. Neither mAblb nor pAbllb/llla had any effect on ADP stimulated platelet aggregation. Concentrations of mAblb and pAbllb/llla which produced half maximal inhibition alone were combined resulting in complete inhibition of TCIPA. Preincubation of MS5I7 and W256 with mAblb also resulted in inhibition of TCIPA, while preincubation of Clone A with mAblb did not, suggesting the presence of this glycoprotein on the cell membranes of MS5I7 and W256, but not on Clone A. Immunofluorescence studies confirmed the presence of this glycoprotein on the cell plasma membrane of the MS5I7 and W256, but not on Clone A. Preincubation of MS5I7 and W256 with both mAblb and pAbllb/llla alone or in combination, also resulted in decreased (12S)-12 -hydroxy -5, 8,10, 14 -eicosatetraenoic acid (12-HETE) production, while platelets preincubated with these antibodies had no effect on the concentration of 12-HETE produced. Isolation of platelet membranes and released platelet contentswere tested separately and in combination on platelet adhesion to ECM. Platelet release factors were ineffective, while isolated platelet membrane ghosts enhanced adhesion. Disruption of the platelet cytoskeleton andinhibition of the formation of the llb/llla complex decreased platelet enhanced tumor cell adhesion. These findings suggest a role for these platelet glycoproteins in TCIPA, platelet enhanced tumor cell adhesion to ECM and subsequent tumor metastasis.

scholarly journals Targeting tumor cell motility as a strategy against invasion and metastasis

2013 ◽  
Vol 34 (5) ◽  
pp. 283-289 ◽  
Author(s):  
Alan Wells ◽  
Jelena Grahovac ◽  
Sarah Wheeler ◽  
Bo Ma ◽  
Douglas Lauffenburger
Keyword(s):  
Tumor Cell ◽  
Cell Motility ◽  
Invasion And Metastasis ◽  
Tumor Cell Motility

scholarly journals Syndecan-4 in Tumor Cell Motility

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3322
Author(s):  
Aniko Keller-Pinter ◽  
Szuzina Gyulai-Nagy ◽  
Daniel Becsky ◽  
Laszlo Dux ◽  
Laszlo Rovo
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Tumor Cell ◽  
Cell Motility ◽  
Small Gtpase ◽  
Cellular Polarity ◽  
General Role ◽  
Tumor Cell Motility ◽  
Extracellular Matrix Components

Syndecan-4 (SDC4) is a ubiquitously expressed, transmembrane proteoglycan bearing heparan sulfate chains. SDC4 is involved in numerous inside-out and outside-in signaling processes, such as binding and sequestration of growth factors and extracellular matrix components, regulation of the activity of the small GTPase Rac1, protein kinase C-alpha, the level of intracellular calcium, or the phosphorylation of focal adhesion kinase. The ability of this proteoglycan to link the extracellular matrix and actin cytoskeleton enables SDC4 to contribute to biological functions like cell adhesion and migration, cell proliferation, cytokinesis, cellular polarity, or mechanotransduction. The multiple roles of SDC4 in tumor pathogenesis and progression has already been demonstrated; therefore, the expression and signaling of SDC4 was investigated in several tumor types. SDC4 influences tumor progression by regulating cell proliferation as well as cell migration by affecting cell-matrix adhesion and several signaling pathways. Here, we summarize the general role of SDC4 in cell migration and tumor cell motility.

Gastrin-releasing peptide mediates its morphogenic properties in human colon cancer by upregulating intracellular adhesion protein-1 (ICAM-1) via focal adhesion kinase

2007 ◽  
Vol 292 (1) ◽  
pp. G182-G190 ◽  
Author(s):  
Lauren Taglia ◽  
Damien Matusiak ◽  
Kristina A. Matkowskyj ◽  
Richard V. Benya
Keyword(s):  
Extracellular Matrix ◽  
Tumor Cell ◽  
Cell Motility ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Basolateral Membrane ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Gastrin Releasing Peptide ◽  
Tumor Cell Motility

Gastrin-releasing peptide (GRP) and its receptor (GRPR) act as morphogens when expressed in colorectal cancer (CRC), promoting the assumption of a better differentiated phenotype by regulating cell motility in the context of remodeling and retarding tumor cell metastasis by enhancing cell-matrix attachment. Although we have shown that these processes are mediated by focal adhesion kinase (FAK), the downstream target(s) of GRP-induced FAK activation are not known. Since osteoblast differentiation is mediated by FAK-initiated upregulation of ICAM-1 (Nakayamada S, Okada Y, Saito K, Tamura M, Tanaka Y. J Biol Chem 278: 45368–45374, 2003), we determined whether GRP-induced activation of FAK alters ICAM-1 expression in CRC and, if so, determined the contribution of ICAM-1 to mediating GRP's morphogenic properties. Caco-2 and HT-29 cells variably express GRP/GRPR. These cells only express ICAM-1 when GRPR are present. In human CRC, GRPR and ICAM-1 are only expressed by better differentiated tumor cells, with ICAM-1 located at the basolateral membrane. ICAM-1 expression was only observed subsequent to GRPR signaling via FAK. To study the effect of ICAM-1 expression on tumor cell motility, CRC cells expressing GRP, GRPR, and ICAM-1 were cultured in the presence and absence of GRPR antagonist or monoclonal antibody to ICAM-1. CRC cells engaged in directed motility in the context of remodeling and were highly adherent to the extracellular matrix, only in the absence of antagonist or ICAM-1 antibody. These data indicate that GRP upregulation of ICAM-1 via FAK promotes tumor cell motility and attachment to the extracellular matrix.

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