George Poste

The Cancer Cell: Dynamic Aspects and Modifications in Cell-Surface Organization

(First of Two Parts) The essential features of tumor cells that distinguish them from their normal counterparts are their ability to proliferate in an uncontrolled fashion, invade normal tissues an...

Lectin-mediated agglutination of murine lymphoma cells. Cell surface deformability and reversibility of agglutination by saccharides.

Agglutination of S49 mouse lymphoma cells by Ricinus communis I agglutinin can be reversed by the competing haptenic saccharide, lactose, soon after agglutination, but after further incubation in the absence of lectin the agglutination reaction could not be reversed by lactose and the cells remained as multicell aggregates. The irreversibility of S49 cell agglutination was time, temperature and lectin concentration dependent and its onset correlated with ultrastructurally observed deformation of adjacent cell surfaces and an increase in the proportion of adjacent cell surface areas in close apposition within multicell aggregates. Pretreatment of S49 cells with cytochalasin B or cytochalasin B plus vinblastine enhanced R. communis I agglutinin-mediated agglutination, while vinblastine alone and fluoride plus azide had essentially no effect. When drug-treated cells were agglutinated and then incubated in lectin-free drug-containing media for various times prior to lactose addition, the drug effects were more pronounced. Cytochalasin B alone or with vinblastine inhibited lactose reversal of S49 cell agglutination compared to the drug-free controls, while fluoride plus azide enhanced hapten reversibility. Electron microscopic analysis revealed that the onset of agglutination irreversibility correlated with cell surface deformation in the drug-treated cells. Cell aggregates that were more readily reversible by lactose (fluoride plus azide) were unchanged or less deformed, while S49 aggregates treated with cytochalasin B plus vinblastine were more deformed compared to controls without drugs. These experiments suggest a role for cell surface deformability as an important secondary effect during lectin-mediated cell agglutination of S49 lymphoma cells.

The Cellular Interactions of Metastatic Tumor Cells with Special Reference to Endothelial Cells and their Basal Lamina-Like Matrix

Major goals in the prevention of cancer deaths are understanding how malignant tumor cells spread from primary sites to establish near or distant metastases and preventing this process from occurring. Metastasis involves a complex sequence of events in which malignant cells invade the surrounding host tissues, penetrate into lymphatics and blood vessels, detach from the primary tumor mass and spread to other sites where they must implant, invade and finally proliferate to form new metastatic colonies (for reviews see 1–8), This sequence is discussed in the reviews cited above; the present article will be limited to a discussion of the final events involved in the formation of hematogenous metastases (8).

In vitro systems for studying the interaction of metastatic tumor cells with endothelial cells and subendothelial basement membranes

Understanding how malignant tumor cells spread from the primary tumor to establish metastases at other sites in the body is a major goal in cancer research. Metastasis involves a complex sequence of events in which malignant cells invade surrounding host tissues, penetrate lymphatics or blood vessels and are transported to distant body sites. The formation of hematogenous metastases requires that blood-borne tumor cells must arrest within the microcirculation by adhesion to the wall of a blood vessel (usually a capillary or post-capillary venule) and subsequently penetrate the vessel wall to reach extravascular tissues where they proliferate to generate metastatic colonies. The literature on this subject is vast. However, the majority of publications are descriptive and merely document the role of the vasculature as a mechanical conduit for the transport of malignant cells from primary tumors arising in different anatomic locations.