Microtubule disruption reduces metastasis more effectively than primary tumor growth
Keyata N Thompson1, Julia A Ju1, Eleanor C Ory1
1Marlene and Stewart Greenebaum NCI Comprehensive Cancer Center, University of Maryland School of Medicine, 655 W. Baltimore Street, Bressler Research Building, Rm 10-029, Baltimore, MD, 21201, USA.
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.
Insights
Vinorelbine, a microtubule-depolymerizing drug, significantly extended metastatic tumor survival in mice by inhibiting microtentacles. This suggests existing therapies may have overlooked anti-metastatic effects.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Clinical cancer imaging primarily assesses tumor growth, neglecting metastatic phenotypes.
- Metastasis involves complex cellular behaviors like microtentacle formation, reattachment, and clustering.
Purpose of the Study:
- To investigate the anti-metastatic effects of the microtubule-depolymerizing drug Vinorelbine.
- To determine if Vinorelbine selectively targets metastatic phenotypes over primary tumor growth.
- To assess the feasibility of detecting Vinorelbine's anti-metastatic response in circulating tumor cells.
Main Methods:
- Treatment of mice with Vinorelbine for 24 hours.
- Analysis of primary tumor survival and metastatic tumor survival.
- Detection of microtentacle inhibition in tumor cells isolated from blood samples within 1 hour of treatment.
Main Results:
- Vinorelbine treatment extended median metastatic tumor survival from 8 to 30 weeks.
- Vinorelbine reduced metastatic phenotypes (microtentacles, reattachment, clustering) more than tumor cell viability.
- Microtentacle inhibition was detectable within 1 hour in circulating tumor cells, feasible with small cell numbers.
Conclusions:
- Targeted microtubule disruption with Vinorelbine can selectively inhibit metastasis.
- Existing FDA-approved therapies may possess overlooked anti-metastatic actions.
- This approach offers a potential strategy for developing novel anti-metastatic treatments.
Related Concept Videos
02:30Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
01:10Drugs that Destabilize Microtubules
01:15Drugs that Stabilize Microtubules
01:45Destabilization of Microtubules
02:17Microtubule Instability
02:17The Tumor Microenvironment