Microtubule polymerization generates microtentacles important in circulating tumor cell invasion

TL;DR

This study reveals that microtubule polymerization drives the formation of microtentacles in circulating tumor cells, which facilitate adhesion to vessel walls during metastasis, offering new insights into cancer spread mechanisms.

Contribution

It demonstrates that microtubule polymerization, rather than sliding, is the main force behind microtentacle formation in CTCs, linking cytoskeletal dynamics to metastatic potential.

Findings

Microtubule polymerization is the primary driver of microtentacle formation.

Microtentacle length and flexibility influence cell adhesion to vessel walls.

Enhanced microtentacle formation promotes tumor cell attachment during metastasis.

Abstract

Circulating tumor cells (CTCs) have crucial roles in the spread of tumors during metastasis. A decisive step is the extravasation of CTCs from the blood stream or lymph system, which depends on the ability of cells to attach to vessel walls. Recent work suggests that such adhesion is facilitated by microtubule (MT)-based membrane protrusions called microtentacles (McTNs). However, how McTNs facilitate such adhesion and how MTs can generate protrusions in CTCs remain unclear. By combining fluorescence recovery after photobleaching (FRAP) experiments and simulations we show that polymerization of MTs provides the main driving force for McTN formation, whereas the contribution of MTs sliding with respect to each other is minimal. Further, the forces exerted on the McTN tip result in curvature, as the MTs are anchored at the other end in the MT organizing center. When approaching vessel walls, McTN curvature is additionally influenced by the adhesion strength between the McTN and wall. Moreover, increasing McTN length, reducing its bending rigidity, or strengthening adhesion enhances the cell-wall contact area and, thus, promotes cell attachment to vessel walls. Our results demonstrate a link between the formation and function of McTNs, which may provide new insight into metastatic cancer diagnosis and therapy.