Journal of Tumor Research
Open Access

Abstract

Immunoglobulin M Distribution and Modular Peptide Interactions in the Stroma of Human Colorectal Adenomas and Adenocarcinomas

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.