E-cadherin Regulates Anchorage-independent Growth and Survival in Oral Squamous Cell Carcinoma Cells

Kantak, Seema S.; Kramer, Randall H.

doi:10.1074/jbc.273.27.16953

Cited by 209 publications

(196 citation statements)

References 54 publications

(36 reference statements)

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“…This is supported by the observations that (a) AT3.1 cells are closely apposed in free suspension aggregates but separated by matrix in agarose gels ( Figure 4A,C), and (b) the adhesion holding together the large spheroids is not immediately reversed upon removal from the gel. Although formation and compaction of spheroids can be mediated by E-cadherin (Kantak and Kramer, 1998;St. Croix et al, 1998) it has been shown that AT2.1 and 3.1 cell lines do not express E-cadherin (Bussemakers et al, 1992).…”

Section: Morphological Differences May Results From the Stress Responsementioning

confidence: 99%

Solid stress facilitates spheroid formation: potential involvement of hyaluronan

et al. 2002

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When neoplastic cells grow in confined spaces in vivo, they exert a finite force on the surrounding tissue resulting in the generation of solid stress. By growing multicellular spheroids in agarose gels of defined mechanical properties, we have recently shown that solid stress inhibits the growth of spheroids and that this growth-inhibiting stress ranges from 45 to 120 mmHg. Here we show that solid stress facilitates the formation of spheroids in the highly metastatic Dunning R3327 rat prostate carcinoma AT3.1 cells, which predominantly do not grow as spheroids in free suspension. The maximum size and the growth rate of the resulting spheroids decreased with increasing stress. Relieving solid stress by enzymatic digestion of gels resulted in gradual loss of spheroidal morphology in 8 days. In contrast, the low metastatic variant AT2.1 cells, which grow as spheroids in free suspension as well as in the gels, maintained their spheroidal morphology even after stress removal. Histological examination revealed that most cells in AT2.1 spheroids are in close apposition whereas a regular matrix separates the cells in the AT3.1 gel spheroids. Staining with the hyaluronan binding protein revealed that the matrix between AT3.1 cells in agarose contained hyaluronan, while AT3.1 cells had negligible or no hyaluronan when grown in free suspension. Hyaluronan was found to be present in both free suspensions and agarose gel spheroids of AT2.1. We suggest that cell -cell adhesion may be adequate for spheroid formation, whereas solid stress may be required to form spheroids when cell -matrix adhesion is predominant. These findings have significant implications for tumour growth, invasion and metastasis.

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Section: Morphological Differences May Results From the Stress Responsementioning

confidence: 99%

Solid stress facilitates spheroid formation: potential involvement of hyaluronan

et al. 2002

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“…Their finding that caspases have the capacity to cleave b-catenin proteolytically at the N-and C-terminal, which will reduce a-catenin binding, release actin filaments and reduce cell -cell interaction, indicates that b-catenin has an important role at a late stage of apoptosis. Studies on oral squamous cell carcinoma cells also indicate that cadherin-mediated adhesion promotes anchorage-independent growth and suppresses apoptosis (Kantak and Kramer, 1998). A functionally intact cadherin-b-acatenin complex in ovarian cancer could make the cancer cells less susceptible to apoptosis and thereby favour growth.…”

Section: Discussionmentioning

confidence: 99%

Wnt-signalling pathway in ovarian epithelial tumours: increased expression of β-catenin and GSK3β

et al. 2003

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Beta-catenin is involved in both cell -cell adhesion and in transcriptional regulation by the Wingless/Wnt signalling pathway. Alterations of components of this pathway have been suggested to play a central role in tumorigenesis. The present study investigated, by immunohistochemistry and immunoblotting, the protein expression and localisation of b-catenin, adenomatous polyposis coli (APC), glycogen synthase kinase 3b (GSK3b) and lymphocyte enhancer factor-1 (Lef-1) in normal human ovaries and in epithelial ovarian tumours in vivo and in vitro. Immortalised human ovarian surface epithelium and ovarian cancer cell cells (OVCAR-3) expressed b-catenin, APC, GSK3b and Lef-1. Nuclear staining of b-catenin and Lef-1 were demonstrated only in OVCAR-3 cells. There were significant increases of b-catenin and GSK3b, while APC was reduced in ovarian cancer compared to the normal ovary. Beta-catenin and Lef-1 were coimmunoprecipitated in ovarian tumours, but not in the normal ovary. Nuclear localisation of b-catenin or Lef-1 could not be demonstrated in the normal ovary or in the ovarian tumours. The absence of nuclear localisation of b-catenin could be due to an increased binding to the cadherin -a-catenin cell adhesion complex. In fact, we have earlier reported an increased expression of E-cadherin in ovarian adenocarcinomas. In summary, this study demonstrates an increase in the expression of components of the Wingless/Wnt pathway in malignant ovarian tumours. The increase suggests a role for this signalling pathway in cell transformation and in tumour progression. However, it remains to be demonstrated whether it is an increased participation of b-catenin in transcriptional regulation, or in the stabilisation of cellular integrity, or both, that is the crucial event in ovarian tumorigenesis.

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“…During the process of metastasis, intercellular contact mediated through the cell adhesion molecule E-cadherin appears to prevent apoptosis (Kantak and Kramer, 1998;Day et al, 1999). There is growing evidence to suggest that osteopontin may also inhibit apoptosis during metastasis.…”

Section: Discussionmentioning

confidence: 99%

Osteopontin expression correlates with adhesive and metastatic potential in metastasis-inducing DNA-transfected rat mammary cell lines

Moye¹,

Barraclough²,

West

et al. 2004

Br J Cancer

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A metastatic phenotype can be induced in benign rat mammary cells (Rama 37 cells) by transfecting them with metastasis-inducing DNAs (Met-DNAs). Stable transfection of Met-DNAs increases the level of the metastasis-associated protein, osteopontin. Randomly picked clonal cell lines have been established from the pool of Rama 37 cells transfected with one metastasis-inducing DNA, C9-Met-DNA. In these cell lines, moderate correlation is observed between the copy number of C9-Met-DNA and their metastatic potential (linear regression coefficient, R 2 ¼ 0.48). A very close correlation is observed between the cell lines' metastatic potential in vivo and the osteopontin mRNA levels in vitro (R 2 ¼ 0.74), but not with another metastasis-associated protein in this system, S100A4 (R 2 ¼ 0.21). A close correlation is also observed between osteopontin mRNA levels and the adhesive potential (R 2 ¼ 0.91) of the cells, but not with their growth rate in vitro (R 2 ¼ 0.03). These observations support the previous suggestion that osteopontin is the direct effector of C9-Met-DNA and that the presence of C9-Met-DNA is necessary, if not sufficient, for the induction of metastasis in vivo in this system. Additionally, these results suggest that Rama 37 cells with increased osteopontin mRNA levels become metastatic not through an increased growth rate, but through an increase in cellular adhesiveness.

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E-cadherin Regulates Anchorage-independent Growth and Survival in Oral Squamous Cell Carcinoma Cells

Cited by 209 publications

References 54 publications

Solid stress facilitates spheroid formation: potential involvement of hyaluronan

Solid stress facilitates spheroid formation: potential involvement of hyaluronan

Wnt-signalling pathway in ovarian epithelial tumours: increased expression of β-catenin and GSK3β

Osteopontin expression correlates with adhesive and metastatic potential in metastasis-inducing DNA-transfected rat mammary cell lines

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