The integrins are a family of integral membrane receptors that participate in binding to various extracellular and cell surface proteins during adhesion, migration, and homing of normal and neoplastic cells. In this study, we characterized the involvement of integrins in mediating the growth of an adhesion-dependent gastric adenocarcinoma line, ST2. This line was distinguished and selected for study based on its inability to grow when suspended in soft agar or plated on poly(2-hydroxyethyl methacrylate)-coated dishes. ST2 cells arrested in G0/G1 of the cell cycle when deprived of adhesion to substrate. Using purified matrix components, collagen was found to be highly active in promoting beta 1 integrin-mediated cell attachment and spreading. Subsequent to spreading on collagen, the cells were released from G0/G1 block and progressed into S phase. Monoclonal antibodies to alpha 2 or beta 1 integrin blocked the reinduction of both cell spreading and entry into S phase. These studies suggest that during the metastatic process, integrin receptor interaction with the insoluble matrix may be an important step leading to proliferation of some tumors.

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There is strong evidence that multistep tumorigenesis begins with the acquisition of somatic mutations which promote genomic instability. Genomic instability is an important malignant trait because genomic instability can generate the genetic diversity that is necessary for the transforming cell to acquire increasingly variable and aggressive tumor phenotypes. Genomic instability often manifests in the form of chromosomal instability (CIN) leading to the induction of aneuploidy, a phenomenon identified by high resolution molecular cytogenetic techniques. Fluorescent in situ hybridization (FISH) and Array Comparative Genomic Hybridization (aCGH) are two high resolution molecular cytogenetic techniques that allow detection of chromosomal aneuploidy and structural rearrangements occurring in pre-malignant and malignant lesions during tumor progression and invasion. These high resolution molecular cytogenetic techniques are used for genetic screening of single cells in pre-malignant and precursor malignant lesions as well as in exfoliated cells from body fluids and excreta. Consequently, molecular cytogenetic testing offers the promise of an extremely powerful method of risk assessment and early detection of cancer.