Epithelial and mesenchymal phenotypic switchings modulate cell motility in metastasis

Abstract

The most ominous stage of cancer progression is the dissemination of carcinomas from their primary site into adjacent tissues, invasion, or distant ectopic organs, metastasis. These steps renders current extirpative therapies paliative at best and heralds the use of systemic therapies that are curative in only a small subset of patients even using the newest biological agents. This calls for a greater understanding of the tumor biology of tumor progression integrating the carcinoma intrinsic properties with the tissue environmental modulators of behavior. In no aspect of progression is this more evident that the critical step of tumor cell motility that is critical for both escape from the primary mass and seeding into ectopic organs and tissues. In this overview, we discuss how this behavior is modified by carcinoma cell phenotypic plasticity that is evidenced by reversible switching between epithelial and mesenchymal phenotypes. The intercellular linkages or absence thereof dictate the receptivity towards signals from the extracellular milieu. A number of clearly implicated such signals, soluble growth factors and cytokines and extracellular matrix components with embedded matrikines and matricryptines, will be discussed in depth. Finally, we will describe a new mode of discerning the balance between movement as an epithelioid cell and as a mesenchymal-like counterpart.

Partial Mesenchymal to Epithelial Reverting Transition in Breast and Prostate Cancer Metastases

“…These data support earlier experimental evidence that the EMT that allows for escape from the primary lesion is not fixed but can be reverted during metastatic seeding [1,8,9]. However, often pathological examination of large metastases removed for palliative or diagnostic needs present de-differentiated cells reminiscent of the original EMT, which superficially appears at odds with our model of MErT.…”

“…During cancer-associated EMT, loss of cell-cell adhesions via downregulation of E-cadherin allows for both physical detachment from the tumor mass and for external autocrine growth factor and internal signaling that activates cell migration [1]. EMT in cancer progression and metastasis has been widely studied through in vitro cell culture and in vivo animal models of cancer progression.…”

“…In addition, EMT has been visualized at the invasive front of primary carcinomas as individual cells or a group of cells migrating into the surrounding tissue [2]. However, the true extent of EMT in human cancer specimens is still open to debate as is the role of EMT in metastatic seeding [1,3,4].…”

Mechanism of the Mesenchymal–Epithelial Transition and Its Relationship with Metastatic Tumor Formation

“…Epithelial cells acquire fibroblastlike properties and exhibit reduced cell-cell adhesion and increased motility via EMT, which facilitates the escape of tumor cells from primary tumors (5,6). EMT represents a fundamentally important process that is conducive to tumor dissemination, prompting investigators to explore the mechanism of EMT and methods to inhibit or even reverse this process and thereby inhibit tumor metastasis (7).…”

Role of cadherins in health and in developing breast cancer

“…Этот про-цесс схож с таковым, осуществляемым во время эмбрио-нального развития, но его важной отличительной особен-ностью является неконтролируемость [17,28,48]. ЭМП реализуется в эпителиальных опухолях, обеспечивая спо-собность к инвазии и метастазированию [31,36,49].…”