Microtubule disruption reduces metastasis more effectively than primary tumor growth

Abstract

Clinical cancer imaging focuses on tumor growth rather than metastatic phenotypes. The microtubule-depolymerizing drug, Vinorelbine, reduced the metastatic phenotypes of microtentacles, reattachment and tumor cell clustering more than tumor cell viability. Treating mice with Vinorelbine for only 24 h had no significant effect on primary tumor survival, but median metastatic tumor survival was extended from 8 to 30 weeks. Microtentacle inhibition by Vinorelbine was also detectable within 1 h, using tumor cells isolated from blood samples. As few as 11 tumor cells were sufficient to yield 90% power to detect this 1 h Vinorelbine drug response, demonstrating feasibility with the small number of tumor cells available from patient biopsies. This study establishes a proof-of-concept that targeted microtubule disruption can selectively inhibit metastasis and reveals that existing FDA-approved therapies could have anti-metastatic actions that are currently overlooked when focusing exclusively on tumor growth.

Fn14-Directed DART Nanoparticles Selectively Target Neoplastic Cells in Preclinical Models of Triple-Negative Breast Cancer Brain Metastasis

“…Fn14 expression in the murine and human TNBC cell lines selected for these studies was investigated via Western blotting and flow cytometry. MDA-MB-231-TD-luc (231-TD-luc) is a tumor-derived (“TD”) variant of the well-studied MDA-MB-231 TNBC cell line used in our previous efficacy studies that exhibits high metastatic potential . The 66.1-luc cells are murine TNBC cells syngeneic with BALB/c mice .…”

“…MDA-MB-231-TD-luc (231-TD-luc) is a tumor-derived ("TD") variant of the wellstudied MDA-MB-231 TNBC cell line used in our previous efficacy studies 28 that exhibits high metastatic potential. 49 The 66.1-luc cells are murine TNBC cells syngeneic with BALB/c mice. 53 Fn14 protein expression was detected in both cell lines by Western blot analysis (Figure 2A).…”

“…Human MDA-MD-231-TD-luciferase ("231-TD-luc") TNBC cells were provided by Dr. Stuart Martin (University of Maryland School of Medicine (UMSOM)). 49 Cells were cultured in DMEM supplemented with 10% fetal bovine serum (FBS, Invitrogen 16140071), 1% penicillin− streptomycin (1000 units/L, Invitrogen 15140122), 0.25 mg/ mL G418 sulfate (Gemini Bio 400-113), and 0.5 mg/mL hygromycin B (Corning 30-240-CR). Murine 66.1 TNBC cells were provided by Dr. Amy Fulton (UMSOM).…”

The emerging role of microtubules in invasion plasticity

“…In point of fact, the prototypic antimitotic drugs paclitaxel and vincristine can in certain instances promote metastasis ( 163 , 164 ). On the other hand, vinorelbine treatment in mice reduced metastasis more effectively than primary tumor growth ( 165 ). Another microtubule inhibitor, eribulin, exerts migrastatic behavior both in experimental conditions ( 166 , 167 ) and in patients with advanced metastatic breast cancer ( 168 ).…”

High-Efficiency Inertial Separation of Microparticles Using Elevated Columned Reservoirs and Vortex Technique for Lab-on-a-Chip Applications

“…Vortex technology is a passive, high-throughput, and label-free method that relies solely on particle size and physical parameters. , Separated CTCs in this method are intact, pure, and viable for downstream clinical examination. − The processing time for whole blood is short due to optimizing the flow rate and establishing a high-throughput separation mechanism. Additionally, it is cost-effective and automated, requiring no need for a laboratory expert.…”