Human melanoma integrins contribute to arrest and stabilization potential while flowing over extracellular matrix

Abstract

SummaryTo form distatit metastases. tumour cells must stabilize adhesive interactions that prevent detachment at secondary sites. Primary receptor-ligand interactions alone may not maintain prolonged adhesive contacts without secondary events that lead to adhesion stabilization. Computerized imaging methods enable us to examine various substrates for: (i) the wall shear adhesion threshold (WSAT). a measure ofthe dynamic adhesive potential of tumour cells; (ii) the number of tumour cells that adhered; and (iii) the adhesion stabilization lag time (ASLT) or length of time required for tumour cells to stabilize adhesive contacts capable of withstanding high wall shear force (up to 100 dynes/cm-). The relative WSAT ratios found were: wheat germ agglutinin (WGA) > laminin > fibroncctin > vitronectin > collagen I > collagen IV > von Willebrand factor (vWF) (the greater the shear rate the higher the adhesive potential). The relative stabilization ratios found were as follows: laminin < fibronectin < vitronectin < collagen IV < collagen I < vWF < WGA (shorter times correlate with greater stabilization potential). Stabilization data using fibronectin as a substrate correlated the best with metastatic potential. Using three melanoma lines of ditterent metastatic potential semiquantitative reverse transcriptase-polymerase chain reaction (PCR) showed a two-to four-fold increase in al, a3, a4. a5. a6, and ICAM-1 in the highly metastatic 70W celts compared to the MeWo and non-metastatic 3S? melanoma cells. There were no differences in av. p I and p3 levels among the three melanoma lines, and PCR products for allb. a2, CD36. or ICAM-2 were not detected. The 70W cells also had higher levels of ax and p2 (CD11/CD18 and pl50 leukocyte antigen) than either the MeWo or 3S5 cells. The data indicate that melanoma cells exhibit differences in the adhesion properties under fluid shear and differences in the expression of adhesion components that correlate with their metastatic potential.

Tumor cell adhesion of human colon carcinoma cells with different metastatic properties to extracellular matrix under dynamic conditions of laminar flow

“…We also found that speci®c and nonspeci®c tumor cell-ECM interactions may occur in the presence of¯ow comparable to the conditions in the microcirculation, and these interactions were distinct in cells lines with metastatic properties. Similar correlations were previously reported using other cell systems, such as melanoma and large cell lymphoma cells with dierent metastatic behaviors (Menter et al 1995;Menter et al 1992;Yun et al 1997). The dynamic adhesive properties as well as cell adhesion of HT-29 cells under static conditions are apparently mediated to a large degree by b 1 -integrins (Haier 1999c).…”

“…Unfortunately, these assays do not consider hydrodynamic forces, such as wall shear stress (WSS) or the parabolic form of laminar¯ow that occurs within the microvasculature. Using speci®c parallel plate laminar¯ow chambers for hydrodynamic adhesion assays the dierent phases of adhesive interactions between circulating cells and vascular surfaces (EC or ECM) can be studied separately (Menter et al 1995). The conditions of hydrodynamic adhesion in these reports revealed that both biophysical and biochemical interactions were involved in cell adhesion.…”

Chemokine receptors and melanoma metastasis

“…Subsequent studies in our laboratory indicated that activation of CXCR4 increased the affinity of b1 integrin on the B16 cells, leading to greater adherence of this integrin to one of its principal ligands, the endothelial cell adhesion molecule called vascular cell adhesion molecule (VCAM)-1 [25]. Prior studies demonstrated that integrins, especially of the b1 integrin family, play important roles in melanoma invasion and metastasis through enhancement of motility and migration [28,29]. As integrins constitutively exhibit low affinity for their ligands, other cell surface receptors, such as chemokine receptors, must usually be engaged first in order to increase the affinity of the integrin for its ligand [30,31].…”

Role of Tumor Cell Adhesion and Migration in Organ-Specific Metastasis Formation

“…Following the initial adhesive interactions with ECs, TCs have to actively change their shape by spreading or flattening to increase contact areas and initiate cell migration through the vessel wall [48]. Active extravasation enables them to escape the high shear forces within the center of the parabolic curve of fluid flow [49].…”