Adhesion receptors in malignant transformation and dissemination of gastrointestinal tumors.
Adhesion receptors on the surface of cancer cells play an important role in tumor cell migration, invasion, and metastasis. A number of specific cell surface-associated molecules that mediate cell-matrix and cell-cell interactions have been characterized, including the family of integrin receptors, the cadherins, the immunoglobulin (IgG) superfamily, a 67-kDa laminin-binding protein, and the CD44 receptor. Changes in the expression and function of these adhesion molecules are important characteristics in the development of gastrointestinal malignancies and might be used in the future as prognostic factors or as new targets in diagnosis and therapy. In esophageal cancer a downregulation 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. The occurrence of the CD44 standard and the CD44-9v isoform on the surface of gastric cancer cells 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 metastasize in the lymph nodes. In pancreatic cancer the expression of integrin adhesion receptors is significantly altered during the malignant transformation of the pancreatic tissue while a loss of the E-cadherin receptor can generate dedifferentiation and invasiveness of pancreas carcinoma cells. There is increasing evidence that integrin receptors and different isoforms of the CD44 receptor are altered following the malignant transformation of colonic mucosa into adenomas and invasive carcinomas and thus influencing in their metastatic potential. 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 could be observed between the expression of the 67-kDa laminin receptor and the degree of differentiation, the invasive phenotype, and the metastatic abilities of colorectal cancer cells. Analyzing the expression of the E-cadherin receptor in colorectal carcinomas it has been shown that this receptor may serve as an independent prognostic marker in Dukes' stage Colon cancer to identify patients with poor prognosis and designate them for adjuvant therapy after curative surgical treatment.
Dept. of Hematology and Oncology, University Medical Center, Benjamin Franklin, Free University of Berlin, Germany.
M
M
Streit
R
R
Schmidt
R U
RU
Hilgenfeld
E
E
Thiel
E D
ED
Kreuser
D000818:Animals; D015820:Cadherins / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy; D006801:Humans; D018960:Hyaluronan Receptors / Q000502:physiology; D016023:Integrins / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D011379:Prognosis; D017474:Receptors, Laminin / Q000502:physiology
D015820:Cadherins; D015815:Cell Adhesion Molecules; D018960:Hyaluronan Receptors; D016023:Integrins; D017474:Receptors, Laminin; D018799:Intercellular Adhesion Molecule-1