Adhesion receptors in malignant transformation and dissemination of gastrointestinal tumors

Abstract

Changes in the expression and function of adhesion molecules on the surface of cancer cells are important characteristics in the development of gastrointestinal malignancies and might be used in the future as prognostic factors or as new targets for diagnostic and therapeutic approaches. In esophageal cancer a down-regulation of the E-cadherin receptor and the cytoplasmic protein alpha-catenin is associated with tumor dedifferentiation, infiltrative growth and lymph-node metastasis. In gastric cancer a reduction of E-cadherin expression due to gene mutations is restricted to diffuse-type tumors while the occurrence of the CD44-standard and the CD44-9v isoform is significantly related to a higher tumor-induced mortality and a shorter survival time. The CD44-6v isoform is predominantly expressed by intestinal-type gastric carcinomas, giving these tumor cells the ability to perform lymph-node metastasis. In pancreatic cancer the expression of integrin adhesion receptors is significantly altered during the malignant transformation while a loss of the E-cadherin receptor can generate dedifferentiation and invasiveness of pancreas carcinoma cells. There is increasing evidence that integrin receptors as well as different isoforms of the CD44 receptor are altered following the malignant transformation of colonic mucosa into adenomas and invasive carcinomas. The expression of the CD44-6v isoform seems to be associated with an adverse prognosis in colorectal cancer due to the development of tumor metastases. A strong correlation has been observed between the expression of the 67-kDa laminin receptor and the degree of differentiation, the invasive phenotype and the metastatic abilities af colorectal cancer cells. Analyzing the expression of the E-cadherin receptor showed that this receptor may serve as an independent prognostic marker in Dukes' stage B colorectal cancer to identify patients with poor prognosis and designate them for intensive adjuvant therapy and clinical observation after curative surgical tumor treatment.

Expression Profiling Using a cDNA Array and Immunohistochemistry for the Extracellular Matrix Genes FN-1, ITGA-3, ITGB-5, MMP-2, and MMP-9 in Colorectal Carcinoma Progression and Dissemination

“…Thus, the basal membrane and the ECM jointly represent two important physical barriers to malignant invasion, and their degradation by metalloproteinase enzymes may have an important role in tumor progression and metastatic dissemination [2–4]. Other researchers, however, have reported that, in general, the expression levels of integrins alpha 3 and alpha 5 are reduced in many colorectal carcinomas (CRCs) [5, 6]. …”

Tumour-associated E-cadherin mutations alter cellular morphology, decrease cellular adhesion and increase cellular motility

“…Consequently, numerous researchers, including ourselves, have analysed diuse and adhesive-type tumours in order to ®nd dierences in the expression or integrity of cell adhesion molecules, especially E-cadherin (cf. Gabbert et al, 1996;Streit et al, 1996, for reviews).…”

Brain metastases from pancreatic adenocarcinoma

“…Some authors have suggested that expression of certain adhesion molecules by the tumour cells could predetermine their affinity for the CNS 8 , 9. For example, some variant forms of CD44 are preferentially expressed by brain metastases from colon or lung lesions than by primary brain tumours 10…”