Circulating Tumor Cells: Towards Mechanical Phenotyping of Metastasis

Overview

Journal iScience

Publisher Cell Press

Date 2022 Mar 14

PMID 35281737

Authors

Marina Peralta

Nael Osmani

Jacky G Goetz

Affiliations

Soon will be listed here.

Abstract

During cancer progression, metastatic dissemination accounts for ∼90% of death in patients. Metastasis occurs upon dissemination of circulating tumor cells (CTC) through body fluids, in particular the bloodstream, and several key steps remain elusive. Although the majority of CTCs travel as single cells, they can form clusters either with themselves (homoclusters) or with other circulating cells (heteroclusters) and thereby increase their metastatic potential. In addition, cancer cell mechanics and mechanical cues from the microenvironment are important factors during metastatic progression. Recent progress in intravital imaging technologies, biophysical methods, and microfluidic-based isolation of CTCs allow now to probe mechanics at single cell resolution while shedding light on key steps of the hematogenous metastatic cascade. In this review, we discuss the importance of CTC mechanics and their correlation with metastatic success and how such development could lead to the identification of therapeutically relevant targets.

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References

Offeddu G, Hajal C, Foley C, Wan Z, Ibrahim L, Coughlin M . The cancer glycocalyx mediates intravascular adhesion and extravasation during metastatic dissemination. Commun Biol. 2021; 4(1):255. PMC: 7910477. DOI: 10.1038/s42003-021-01774-2. View

Xin Y, Li K, Yang M, Tan Y . Fluid Shear Stress Induces EMT of Circulating Tumor Cells via JNK Signaling in Favor of Their Survival during Hematogenous Dissemination. Int J Mol Sci. 2020; 21(21). PMC: 7663710. DOI: 10.3390/ijms21218115. View

Cristofanilli M, Budd G, Ellis M, Stopeck A, Matera J, Miller M . Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004; 351(8):781-91. DOI: 10.1056/NEJMoa040766. View

Aceto N, Bardia A, Miyamoto D, Donaldson M, Wittner B, Spencer J . Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell. 2014; 158(5):1110-1122. PMC: 4149753. DOI: 10.1016/j.cell.2014.07.013. View

Kumar S, Weaver V . Mechanics, malignancy, and metastasis: the force journey of a tumor cell. Cancer Metastasis Rev. 2009; 28(1-2):113-27. PMC: 2658728. DOI: 10.1007/s10555-008-9173-4. View

Sarioglu A, Aceto N, Kojic N, Donaldson M, Zeinali M, Hamza B . A microfluidic device for label-free, physical capture of circulating tumor cell clusters. Nat Methods. 2015; 12(7):685-91. PMC: 4490017. DOI: 10.1038/nmeth.3404. View

San Juan B, Garcia-Leon M, Rangel L, Goetz J, Chaffer C . The Complexities of Metastasis. Cancers (Basel). 2019; 11(10). PMC: 6826702. DOI: 10.3390/cancers11101575. View

Paoletti C, Miao J, Dolce E, Darga E, Repollet M, Doyle G . Circulating Tumor Cell Clusters in Patients with Metastatic Breast Cancer: a SWOG S0500 Translational Medicine Study. Clin Cancer Res. 2019; 25(20):6089-6097. PMC: 6801082. DOI: 10.1158/1078-0432.CCR-19-0208. View

Choi J, Kim J, Yang Y, Kim P, Yoon K, Yun S . Urokinase exerts antimetastatic effects by dissociating clusters of circulating tumor cells. Cancer Res. 2015; 75(21):4474-82. DOI: 10.1158/0008-5472.CAN-15-0684. View

10.

Kim Y, Koo K, Sung J, Yun U, Kim H . Anoikis resistance: an essential prerequisite for tumor metastasis. Int J Cell Biol. 2012; 2012:306879. PMC: 3296207. DOI: 10.1155/2012/306879. View

11.

Ocana O, Corcoles R, Fabra A, Moreno-Bueno G, Acloque H, Vega S . Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell. 2012; 22(6):709-24. DOI: 10.1016/j.ccr.2012.10.012. View

12.

Gascoyne P, Shim S . Isolation of circulating tumor cells by dielectrophoresis. Cancers (Basel). 2014; 6(1):545-79. PMC: 3980488. DOI: 10.3390/cancers6010545. View

13.

Mammadova-Bach E, Zigrino P, Brucker C, Bourdon C, Freund M, De Arcangelis A . Platelet integrin 61 controls lung metastasis through direct binding to cancer cell-derived ADAM9. JCI Insight. 2016; 1(14):e88245. PMC: 5033851. DOI: 10.1172/jci.insight.88245. View

14.

Follain G, Osmani N, Azevedo A, Allio G, Mercier L, Karreman M . Hemodynamic Forces Tune the Arrest, Adhesion, and Extravasation of Circulating Tumor Cells. Dev Cell. 2018; 45(1):33-52.e12. DOI: 10.1016/j.devcel.2018.02.015. View

15.

Ortiz-Otero N, Clinch A, Hope J, Wang W, Reinhart-King C, King M . Cancer associated fibroblasts confer shear resistance to circulating tumor cells during prostate cancer metastatic progression. Oncotarget. 2020; 11(12):1037-1050. PMC: 7105166. DOI: 10.18632/oncotarget.27510. View

16.

Caramel J, Papadogeorgakis E, Hill L, Browne G, Richard G, Wierinckx A . A switch in the expression of embryonic EMT-inducers drives the development of malignant melanoma. Cancer Cell. 2013; 24(4):466-80. DOI: 10.1016/j.ccr.2013.08.018. View

17.

Chen M, Whisler J, Jeon J, Kamm R . Mechanisms of tumor cell extravasation in an in vitro microvascular network platform. Integr Biol (Camb). 2013; 5(10):1262-71. PMC: 4038741. DOI: 10.1039/c3ib40149a. View

18.

Follain G, Osmani N, Gensbittel V, Asokan N, Larnicol A, Mercier L . Impairing flow-mediated endothelial remodeling reduces extravasation of tumor cells. Sci Rep. 2021; 11(1):13144. PMC: 8222393. DOI: 10.1038/s41598-021-92515-2. View

19.

Lambert A, Pattabiraman D, Weinberg R . Emerging Biological Principles of Metastasis. Cell. 2017; 168(4):670-691. PMC: 5308465. DOI: 10.1016/j.cell.2016.11.037. View

20.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View