Altered Antigen Expression Predicts Outcome in Squamous Cell Carcinoma of the Head and Neck

Wolf, Gregory T.; Carey, Thomas E.; Schmaltz, Stephen; McClatchey, Kenneth D.; Poore, Judy; Glaser, Lynda; Hayashida, Diana J. S.; Hsu, Sandra

doi:10.1093/jnci/82.19.1566

Cited by 91 publications

(57 citation statements)

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“…These findings suggest that the avidity ofcolon carcinoma adhesion to laminin is determined by the expression ofthe a6ß4 integrin. Indirect support ofthis possibility comes from several studies that have correlated 04 expression with the invasive and metastatic behavior of tumor cells (Falcioni et al, 1986;Kimmel and Carey, 1986;Wolf et al, 1990) . In particular, it is worth noting the compelling report that 04 expression (A9 antigen) is a predictive marker of the lethality of squamous cell carcinomas (Wolf et al, 1990) .…”

Section: Discussionmentioning

confidence: 98%

“…Indirect support ofthis possibility comes from several studies that have correlated 04 expression with the invasive and metastatic behavior of tumor cells (Falcioni et al, 1986;Kimmel and Carey, 1986;Wolf et al, 1990) . In particular, it is worth noting the compelling report that 04 expression (A9 antigen) is a predictive marker of the lethality of squamous cell carcinomas (Wolf et al, 1990) . In vitro studies by the same group have implicated a6ß4 as a squamous carcinoma laminin receptor based on GoH3 inhibition of laminin adhesion and the lack of detectable a6ß1 expression (Van Waes et al ., 1991) .…”

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

The integrin alpha 6 beta 4 is a laminin receptor.

Lee

Lotz

Steele

et al. 1992

The Journal of Cell Biology

286

168

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Abstract. In this study, the putative laminin receptor function of the a6ß4 integrin was assessed . For this purpose, we used a human cell line, referred to as clone A, that was derived from a highly invasive, colon adenocarcinoma . This cell line, which expresses the a6ß4 integrin, adheres to the ES and not to the PI fragment of laminin . The adhesion of clone A cells to laminin is extremely rapid with half-maximal adhesion observed at 5 min after plating . Adhesion to laminin is blocked by GoH3, an a6 specific antibody (60% inhibition), as well as by A9, a 04 specific antibody (30% inhibition) . Most importantly, we demonstrate that a6ß4 binds specifically to laminin-

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

The integrin alpha 6 beta 4 is a laminin receptor.

Lee

Lotz

Steele

et al. 1992

The Journal of Cell Biology

286

168

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“…In further studies, the tumor antigens TSP-180 and A9 were found to be identical to ␣6␤4 (39, 93). Increased expression of ␣6␤4 and changes in its distribution were then correlated with increased aggressiveness of tumors and poor prognosis (15,97). At the same time, ␣6␤4 was also found to be a component of HDs (34,84,87).…”

Section: History Of the ␣6␤4 Integrinmentioning

confidence: 99%

Multiple Functions of the Integrin α6β4 in Epidermal Homeostasis and Tumorigenesis

Wilhelmsen

Litjens

Sonnenberg

2006

Molecular and Cellular Biology

126

135

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Since the discovery of the ␣6␤4 integrin in the late 1980s, our understanding of its role in providing stable adhesion of epithelial cells to basement membranes (BM) has significantly increased. ␣6␤4 plays a key role in the formation and stabilization of junctional adhesion complexes called hemidesmosomes (HDs) that are connected to the intermediate filament (IF) system, as well as in the regulation of a variety of signaling processes. However, it is not clear as yet whether ␣6␤4 participates in cell signaling by serving as a substrate for tyrosine kinases and as an adaptor for their associated signaling proteins or whether its role in cellular processes is passive, involving regulation of the assembly and disassembly of HDs. In this review, we will discuss the roles attributed to ␣6␤4 and the controversies in the field. HISTORY OF THE ␣6␤4 INTEGRINThe integrin ␣6␤4 was discovered in the late 1980s by two different groups and was called either ␣E␤4 or Ic-Ic binding protein (Ic-IcBP) (36, 85). The Ic subunit had previously been shown to form a complex with glycoprotein IIa on platelets (86), which was subsequently identified as the common ␤1 subunit of the integrin family (63). Since the Ic subunit was immunologically and biochemically different from the five integrin ␣ subunits known at that time, it was named ␣6 and the complex of ␣6 with ␤1 was called VLA-6 (30). Subsequently IcBP, which for an integrin subunit had the unusual size of approximately 200 kDa, was found to be identical to the ␤4 subunit of the ␣E␤4 complex (29). The discovery of the integrin ␣6␤4 demonstrated that a particular ␣ subunit can dimerize with more than one ␤ subunit, a property that was then thought to be unique for ␤ subunits. In further studies, the tumor antigens TSP-180 and A9 were found to be identical to ␣6␤4 (39, 93). Increased expression of ␣6␤4 and changes in its distribution were then correlated with increased aggressiveness of tumors and poor prognosis (15,97). At the same time, ␣6␤4 was also found to be a component of HDs (34,84,87). Although ␣6␤4, like ␣6␤1, can interact with different laminin isoforms, its preferred ligand in the epidermal BM is laminin-5 (4, 57, 71).Sequencing of ␤4 revealed that its large size is due to an unusually long cytoplasmic domain of over 1,000 amino acids (31,89). This domain contains two pairs of type III fibronectin (FNIII) domains, separated by a connecting segment (CS) (Fig. 1). A Na-Ca exchanger (CalX) motif precedes the first FNIII domain, but its function is still not clear (77). Importantly, ␣6␤4 was found to be associated with keratin IFs instead of with actin like other integrins (26, 84). The association with IFs is mediated by the hemidesmosomal components plectin and BP230 (27,58,70). The importance of ␤4 for adhesion to the BM became evident in ␤4 knockout mice that developed severe blistering of the skin (14, 92). This was in line with findings, just prior to these studies, that a mutation in the ␤4 gene (ITGB4) is responsible for the pyloric atresia associated with junctional ...

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“…It has been suggested that ao6 expression is a possible grading parameter for oral SCC and that tumors with a propensity to metastasize to regional lymph nodes display (X6134 positivity. Attempts to relate this integrin to tumor prognosis, however, have been largely unsuccessful (Wolf et al, 1990;Cortesina et al, 1995;Kosmehl et al, 1995). Garzino-Demo et al (1998) found aberrant expression of (x6 in oral SCC and suggested that the lack of restricted basal polarization of (x6 could be an early marker of oral malignancy.…”

Section: Integrins In Tumorsmentioning

confidence: 99%

Cell Adhesion Molecules and Oral Cancer

Thomas

Speight

2001

Critical Reviews in Oral Biology & Medicine

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Cell adhesion molecules (CAMs) are found on the surfaces of all cells, where they bind to extracellular matrix molecules or to receptors on other cells. As well as having a structural role, CAMs function as signaling receptors, transducing signals initiated by cellular interactions which regulate many diverse processes, including cell division, migration, and differentiation. Cell adhesion molecules are essential for maintaining stable tissue structure. However, cell adhesion must be dynamic to facilitate the mobility and turnover of cells. In dynamic situations, cells alter their cell-cell and cell-matrix interactions by virtue of altered expression and function of CAMs. The expression of CAMs is normally tightly regulated, thereby controlling cell proliferation, mobility, differentiation, and survival. Many of these processes are misregulated in malignant tumors, and it has been shown that many of the characteristics of tumor cells are attributable to the aberrant expression or function of CAMs.Integrins and E-cadherin are the most important CAMs expressed by stratified squamous epithelium. Altered expression of these molecules has been found in oral carcinoma, where loss of CAM expression is often seen in poorly differentiated lesions.However, up-regulation of certain integrins, such as av16, has consistently been found in oral cancer, suggesting that it may play an active role in disease progression.Key words. Oral cancer, cell adhesion molecules, integrins, cadherins, selectins, immunoglobulin superfamily, CD44. (I) IntroductionCell adhesion molecules (CAMs) are found on the surfaces of all cells, where they bind to extracellular matrix molecules or to receptors on other cells. Cell adhesion is critical in the dynamic processes necessary for tissue morphogenesis in development and the maintenance of complex differentiated tissues in adult organisms. CAMs serve in these roles by virtue of their capacity to connect the exterior of the cell with the interior. They form structural linkages between the cell cytoskeleton and the extracellular matrix or between cells, and also function as signaling receptors, transducing signals initiated by cellular interactions which regulate many diverse processes, including cell division, migration, and differentiation ( Fig. 1).Cell adhesion molecules are essential for maintaining the stable structure of stratified squamous epithelium. In normal epithelium, keratinocytes are attached to each other and to the underlying basement membrane. Cell adhesion, however, must be dynamic to facilitate the mobility and turnover of cells. In dynamic situations, keratinocytes alter their cell-cell and cell-ECM interactions by virtue of altered expression and function of CAMs.The expression of cell adhesion molecules is normally tightly regulated-forming, persisting, or declining in an ordered fashion. This allows for controlled cell proliferation, mobility, differentiation, and survival. Many of these processes are misregulated in malignant tumors, and it has been shown that man...

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Altered Antigen Expression Predicts Outcome in Squamous Cell Carcinoma of the Head and Neck

Cited by 91 publications

References 0 publications

The integrin alpha 6 beta 4 is a laminin receptor.

The integrin alpha 6 beta 4 is a laminin receptor.

Multiple Functions of the Integrin α6β4 in Epidermal Homeostasis and Tumorigenesis

Cell Adhesion Molecules and Oral Cancer

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