ஐ.எஸ்.எஸ்.என்: 2684-1258
Caterina Defendenti, Fabiola Atzeni, Sandro Ardizzone, Paolo Declich, Simone Saibeni, Emanuela Nebuloni, Simona Bollani, Savino Bruno, Valeria Lucini, Piero Luigi Almasio and Piercarlo Sarzi-Puttini
Background: Tissue organisation field theory explains that cancer starts as a result of an alteration in supporting tissue and inflammatory cells. The immunoglobulins (Igs) detected in colorectal adenocarcinomas come from the loss of integrity of resident μ chain-producing cells. Nearly half of the contact residues of Igs are aromatic and highly reactive. In the same way, the vast majority of cell surface proteins in the extra-cellular matrix contain a number of different domains or modules. The (Arg-Gly-Asp) RGD receptor domain of fibronectin constitutes cell adhesion receptors for cell-matrix adhesion and for bidirectional signaling across the membrane. Highly homologous oligopeptides emulate and compete with matrix adhesive proteins: Streptavidin binds to cells via the (Arg-Tyr- Asp) RYD mimetic RGD peptide. Furthermore, tyrosine-tryptophan-threonine-aspartic acid (YWTD) domains, physiologically binds laminin and seven different endocytic receptors contain 1-8 YWTD beta-propeller domains.
Objective: The primary aim of this study was to evaluate the in situ presence and distribution of μ chains in 46 colorectal tumors of different histological grades using fluoresceinate goat anti-human μ chains. The secondary aim was to evaluate the cell and stromal interactions of the fluoresceinate YWTD, RGD antigens and streptavidin in sequential biopsy specimens of the same samples.
Results: The detection of μ chains was low in the adenomas and high in the adenocarcinomas. Two morphological types of B cells differently associated with tissue integrity. Only stromal μ chain-producing cells strongly bound YWTD, RGD and streptavidin.
Conclusion: In colorectal tumors, RGD-mimicking site peptides mainly compete with fibronectin/immunoglobulin binding. The presence of μ chain/YWTD interactions shows that sequences richer in aromatic residues should be considered.