Human tumor spontaneous metastasis in immunosuppressed newborn rats. I. Characterization of the bioassay

Bailly, Maryse; Bertrand, S.; Doré, Jean‐François

doi:10.1002/ijc.2910490325

Cited by 20 publications

(24 citation statements)

References 16 publications

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“…CMP-[~4C]NeuAc was purchased from Amersham (Les Ulis, France, 10.5 GBq/mmol). Anti-thymocyte serum (ATS) was prepared according to Bailly et al [19].…”

Section: Reference Compounds and Reagentsmentioning

confidence: 99%

“…The procedures for selection and cloning and the culture conditions have been described elsewhere [18,20]. Cell cultures were regularly tested for absence of mycoplasma and preserved metastatic capability.…”

Section: Cells and Cell Culturementioning

confidence: 99%

“…Cell cultures were regularly tested for absence of mycoplasma and preserved metastatic capability. The metastasis incidence and the number of lung nodules in immunosuppressed newborn rats were assessed using a standardized protocol as described [18,19]. …”

Section: Cells and Cell Culturementioning

confidence: 99%

“…In vivo experiments were performed according to Bailly et al [18,19]. Briefly, newborn rats less than 24 hours old received simultaneously an s.c. injection of 0.1 ml melanoma cell suspension ( 106 cells) in the ventral area and an optimal dose of anti-thymocyte serum (ATS) in the dorsal area.…”

Section: Tumors and Metastasesmentioning

confidence: 99%

“…In a spontaneous metastasis model of human melanoma recently established in our laboratory [18,19], PNA-binding glycoproteins are expressed in human melanoma cells able to give lung metastases whereas these cell surface glycoproteins in non-metastatic cells are sialylated and do not bind PNA lectin [20]. Sialyltransferases being also essential enzymes in the biosynthesis of gangliosides, we determined the patterns of gangliosides of metastatic (T 1 C3) and non-metastatic (IC8) clones of our melanoma model, as well as those of the corresponding tumors grown in immunosuppressed newborn rats.…”

Section: Introductionmentioning

confidence: 99%

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Deficiency of ganglioside biosynthesis in metastatic human melanoma cells: relevance of CMP‐NeuAc: LacCer α2‐3 sialyltransferase (GM3 synthase)

et al. 1995

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The glycosphingolipid patterns were analyzed on two clones derived from a human melanoma cell line and selected for their respectively high and low metastatic ability in immunosuppressed newborn rats. Conversely to the weakly metastatic cells which exhibited a pattern similar to that of the parental cell line, highly metastatic human melanoma cells appeared to be deficient in ganglioside biosynthesis. An accumulation of lactosylceramide was found in the latter cells, with low amounts of GM3 as the only ganglioside detected and a fourfold decreased activity of GM3 synthase (EC 2.4.99.9). After subcutaneous injection of metastatic cells in newborn rats, the cells proliferating in the tumor induced at the injection site re-expressed the four common gangliosides of melanoma: GM3, GM2, GD3 and GD2, whereas the cells growing in the lungs as metastatic nodules were deficient in ganglioside synthesis and showed an accumulation of lactosylceramide. Taken together, our results suggest that the human melanoma cells which are able to escape from the primary tumor and invade the lungs have an impaired ganglioside biosynthesis with a deficient GM3 synthase.

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“…CMP-[~4C]NeuAc was purchased from Amersham (Les Ulis, France, 10.5 GBq/mmol). Anti-thymocyte serum (ATS) was prepared according to Bailly et al [19].…”

Section: Reference Compounds and Reagentsmentioning

confidence: 99%

Section: Cells and Cell Culturementioning

confidence: 99%

Section: Cells and Cell Culturementioning

confidence: 99%

Section: Tumors and Metastasesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Deficiency of ganglioside biosynthesis in metastatic human melanoma cells: relevance of CMP‐NeuAc: LacCer α2‐3 sialyltransferase (GM3 synthase)

et al. 1995

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Overexpression of laminin ?1 chain in colonic cancer cells induces an increase in tumor growth

et al. 2001

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Laminins represent a growing family of glycoproteins constituting the basement membrane. They are known to direct many biological processes. With respect to carcinogenesis, laminins play an important role in cell adhesion, mitogenesis, differentiation and even metastasis. To further study the biological significance of laminin-1 (composed of ␣1, ␤1 and ␥1 chains) in intestinal cell differentiation or tumorigenesis, an ␣1-laminin expression vector was introduced into the HT29 colonic cancer cells, in which laminin ␣1 chain is not expressed. Upon transfection of the ␣1 chain, the ␣1␤1␥1 trimer was found secreted in the media along with free Key words: laminins; basement membrane; colonic cancer cells; tumor growth; differentiationIt is well established that in multicellular organisms, extracellular matrix molecules control various physiologic activities such as cell growth, migration, apoptosis and differentiation. The extracellular network includes the interstitial matrix and basement membranes. The basement membranes that separate the connective tissue from epithelia, muscle fibers, blood vessels and nerves are formed by a complex set of collagens and of noncollagenous glycoproteins such as laminins, nidogen and of proteoglycans, which have a unique composition in each organ. Laminins are multifunctional molecules forming a family of proteins that display organ, site and developmental specificity. 1,2 The first characterized laminin isoform, laminin-1 (composed of ␣1, ␤1 and ␥1 chains), is a crosslike-shaped molecule assembled into a triplestranded coiled-coil structure designated as the long arm. 3 As for the other extracellular matrix molecules, laminin-1 is made up of specific structural domains that allow self-assembly, permit interaction with other basement membrane molecules and encode information for the cells via specific transmembrane receptors, mostly of the integrin family. 4 Recent studies performed on various organs during development show that laminin-1 has a rather limited expression. 5 Despite such restricted expression, crucial roles for laminin-1 in organ development and in cell differentiation have been demonstrated by cell-coating experiments, blocking antibody and antisense strategies. Several major functions have been assigned to the constitutive ␣1 chain of laminin-1, among which are the polarization of developing kidney tubules, 6,7 lung alveolar formation, 8 development of submandibular glands 9 and polarization and functional differentiation of mammary and intestinal cells. 10,11 Conversely, alterations in cell-matrix and cell-cell interactions have been shown in a number of pathologic situations, such as inflammatory processes, wound healing and malignant transformation. In colorectal cancer, perturbations in the production, deposition and degradation of matrix molecules, among which are laminins, have been observed. [12][13][14][15][16] The role of laminin-1 in tumor growth and metastasis has been evaluated in several cell systems. In particular, it was shown that coinjection of puri...

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The role of fibroblasts in the modulation of integrin‐dependent interactions between the gastric cell line HGT‐1 and fibronectin

Nejjari

Anderson

Pourreyron

et al. 2004

Intl Journal of Cancer

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Fibronectin plays an important role in gastric cancer progression. However, little is known about the microenvironmental factors modulating integrin-dependent interactions between gastric cancer cells and fibronectin. We therefore studied the regulation by fibroblasts of the integrin-dependent adhesion and migration of the gastric cancer cell line HGT-1 onto fibronectin. We first determined, by immunofluorescence, immunoblotting and flow cytometry, that HGT-1 cells expressed ␣3, ␣5, ␣6, ␣V and ␤1 integrin chains, and the ␣V␤3 and ␣V␤5 dimers. We verified that HGT-1 cells xenografted to the immunosuppressed newborn rat retained the integrin repertoire detected in vitro and were able to induce the formation of tumors rich in fibronectin. By using an in vitro assay in the presence of neutralizing antibodies, we verified that HGT-1 adhesion and migration onto fibronectin involved ␤1, ␣V and ␣5 integrin chains; we verified, by using an in situ adhesion test to rat gastric wall frozen sections, that in situ HGT-1 adhesion to fibronectin was integrin dependent. In coculture experiments, we showed that organ-specific fibroblasts from stomach, lung and dermis were able to induce, in a site-specific manner, the expression of ␤1, ␣5 and ␣V integrin chains in HGT-1 cells, their integrin-dependent adhesion and migration on fibronectin and their capacity to secrete oncofetal fibronectin. In conclusion, our results show the capacity for tissue-derived fibroblasts to modulate the integrin-dependent interactions between the gastric cell line HGT-1 and fibronectin. They strongly suggest that, in gastric cancer, stromal fibroblasts contribute to promote fibronectin-mediated local invasion by tumor cells. © 2004 Wiley-Liss, Inc. Key words: gastric cancer; integrins; fibronectin; stroma; fibroblastsFibronectin is likely to play an important role in gastric cancer progression. [1][2][3][4][5] Histopathological studies strongly suggest that the presence of large amounts of fibronectin in the pericellular matrix is topographically associated with the front of invasion of gastric adenocarcinomas and is clinically correlated with an increased risk of local invasion and metastasis. 1,6 -10 In keeping with these observations, experimental in vitro and in vivo studies using various gastric cancer cell lines have confirmed the critical role played by fibronectin in promoting gastric cancer cell migration and metastasis, through the involvement of specific receptors, including integrin ␣5␤1. 2,3,5,11,12 In gastric cancer, complex functional interactions occur between tumor cells and fibronectin. So far, much attention has been devoted to the capacity for gastric cancer cells to contribute to fibronectin synthesis and degradation. In particular, it has been shown that, in contrast to most other carcinoma cells, gastric cancer cells are able to synthesize and secrete various fibronectin-degrading enzymes, including certain metalloproteases and trypsin, which, in turn, promote their invasive and metastatic capacities. 2,4,11 In contrast, little...

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Human tumor spontaneous metastasis in immunosuppressed newborn rats. I. Characterization of the bioassay

Cited by 20 publications

References 16 publications

Deficiency of ganglioside biosynthesis in metastatic human melanoma cells: relevance of CMP‐NeuAc: LacCer α2‐3 sialyltransferase (GM3 synthase)

Deficiency of ganglioside biosynthesis in metastatic human melanoma cells: relevance of CMP‐NeuAc: LacCer α2‐3 sialyltransferase (GM3 synthase)

Overexpression of laminin ?1 chain in colonic cancer cells induces an increase in tumor growth

The role of fibroblasts in the modulation of integrin‐dependent interactions between the gastric cell line HGT‐1 and fibronectin

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