TY - JOUR

T1 - Biochemical mechanisms of tumor invasion and metastases

AU - Liotta, L A

AU - Wewer, U

AU - Rao, N C

AU - Schiffmann, E

AU - Stracke, M

AU - Guirguis, R

AU - Thorgeirsson, U

AU - Muschel, R

AU - Sobel, M

PY - 1988/1/1

Y1 - 1988/1/1

N2 - Cancer invasion and metastases is a complex multistep process. In order for a tumor cell to successfully traverse all the steps of this process and initiate a metastatic colony, it must express the right combination of gene products. Such gene products may include proteins which regulate cell interaction with the basement membrane and cell motility. Tumor cells attach to the basement membrane glycoprotein laminin via the cell surface laminin receptor. The human laminin receptor was purified and molecularly cloned. The level of laminin receptor mRNA is a variety of human carcinoma cells correlated with the number of laminin receptors on the cell surface of these cells. Following attachment to the basement membrane, the tumor cell next secretes proteases which may degrade type IV collagen. A genetic linkage between type IV collagenase secretion and metastases was studied using our new genetic system for inducing metastases employing the ras oncogene. Following attachment and local proteolysis, the third step of invasion is tumor cell motility. We have isolated a tumor cell autocrine motility factor (AMF). This factor is secreted by the tumor cells and binds to a cell surface receptor resulting in a profound (greater than 100x) stimulation of cell locomotion. AMF may play a major role in the autonomous invasive behavior of tumor cells.

AB - Cancer invasion and metastases is a complex multistep process. In order for a tumor cell to successfully traverse all the steps of this process and initiate a metastatic colony, it must express the right combination of gene products. Such gene products may include proteins which regulate cell interaction with the basement membrane and cell motility. Tumor cells attach to the basement membrane glycoprotein laminin via the cell surface laminin receptor. The human laminin receptor was purified and molecularly cloned. The level of laminin receptor mRNA is a variety of human carcinoma cells correlated with the number of laminin receptors on the cell surface of these cells. Following attachment to the basement membrane, the tumor cell next secretes proteases which may degrade type IV collagen. A genetic linkage between type IV collagenase secretion and metastases was studied using our new genetic system for inducing metastases employing the ras oncogene. Following attachment and local proteolysis, the third step of invasion is tumor cell motility. We have isolated a tumor cell autocrine motility factor (AMF). This factor is secreted by the tumor cells and binds to a cell surface receptor resulting in a profound (greater than 100x) stimulation of cell locomotion. AMF may play a major role in the autonomous invasive behavior of tumor cells.

KW - Animals

KW - Autocrine Motility Factor

KW - Humans

KW - Laminin

KW - Microbial Collagenase

KW - Neoplasm Invasiveness

KW - Neoplasm Metastasis

KW - Neoplasm Proteins

KW - Neoplasms

KW - Receptors, Immunologic

M3 - Journal article

C2 - 2851925

VL - 233

SP - 161

EP - 169

JO - Advances in Experimental Medicine and Biology

JF - Advances in Experimental Medicine and Biology

SN - 0065-2598

ER -