Eribulin induces tumor vascular remodeling through intussusceptive angiogenesis in a sarcoma xenograft model

Eribulin is a novel microtubule inhibitor that, similar to other types of microtubule inhibitors, induces apoptosis by inhibiting the mitotic division of cells. Besides this direct effect on tumor cells, previous studies have shown that eribulin has the potential to induce tumor vascular remodeling in several different cancers; however, the mechanisms underlying this phenomenon remain unclear. In the present study, we aimed to elucidate whether eribulin is effective against synovial sarcoma, a relatively rare sarcoma that often affects adolescents and young adults, and to histologically investigate the microstructure of tumor vessels after the administration of eribulin. We found that eribulin exhibits potent antitumor activity against synovial sarcoma in a tumor xenograft model and that tumor vessels frequently have intervascular pillars, a hallmark of intussusceptive angiogenesis (IA), after the administration of eribulin. IA is a distinct form of angiogenesis that is involved in normal developmental processes as well as pathological conditions. Our data indicate that IA is potentially involved in eribulininduced vascular remodeling and thereby suggest previously unacknowledged role of IA in regulating the tumor vasculature after eribulin administration. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

Eribulin, a novel microtubule inhibitor, not only induces apoptosis by inhibiting mitotic division of cells, but also has the potential to induce tumor vascular remodeling through mechanisms such as intussusceptive angiogenesis. It exhibits potent antitumor activity against synovial sarcoma and leads to the formation of intervascular pillars in tumor vessels, suggesting a previously unacknowledged role of intussusceptive angiogenesis in regulating tumor vasculature after eribulin administration.