Tunneling Nanotubes, a Novel Mode of Tumor Cell-macrophage Communication in Tumor Cell Invasion

Overview

Journal J Cell Sci

Specialty Cell Biology

Date 2019 Jan 20

PMID 30659112

Citations 63

Authors

Samer J Hanna

Kessler McCoy-Simandle

Edison Leung

Alessandro Genna

John Condeelis

Dianne Cox

Affiliations

Soon will be listed here.

Abstract

The interaction between tumor cells and macrophages is crucial in promoting tumor invasion and metastasis. In this study, we examined a novel mechanism of intercellular communication, namely membranous actin-based tunneling nanotubes (TNTs), that occurs between macrophages and tumor cells in the promotion of macrophage-dependent tumor cell invasion. The presence of heterotypic TNTs between macrophages and tumor cells induced invasive tumor cell morphology, which was dependent on EGF-EGFR signaling. Furthermore, reduction of a protein involved in TNT formation, M-Sec (TNFAIP2), in macrophages inhibited tumor cell elongation, blocked the ability of tumor cells to invade in 3D and reduced macrophage-dependent long-distance tumor cell streaming Using an zebrafish model that recreates macrophage-mediated tumor cell invasion, we observed TNT-mediated macrophage-dependent tumor cell invasion, distant metastatic foci and areas of metastatic spread. Overall, our studies support a role for TNTs as a novel means of interaction between tumor cells and macrophages that leads to tumor progression and metastasis.

Citing Articles

Unveiling the power of mitochondrial transfer in cancer progression: a perspective in ovarian cancer.

Wang C, Xie C J Ovarian Res. 2024; 17(1):233.

PMID: 39580453 PMC: 11585251. DOI: 10.1186/s13048-024-01560-8.

Real-time imaging reveals a role for macrophage protrusive motility in melanoma invasion.

Ramakrishnan G, Miskolci V, Hunter M, Giese M, Munch D, Hou Y J Cell Biol. 2024; 224(2.

PMID: 39570286 PMC: 11586626. DOI: 10.1083/jcb.202403096.

Protective effect of mesenchymal stromal cells in diabetic nephropathy: the In vitro and In vivo role of the M-Sec-tunneling nanotubes.

Barutta F, Corbetta B, Bellini S, Gambino R, Bruno S, Kimura S Clin Sci (Lond). 2024; 138(23):1537-1559.

PMID: 39535903 PMC: 11609313. DOI: 10.1042/CS20242064.

Invisible Bridges: Unveiling the Role and Prospects of Tunneling Nanotubes in Cancer Therapy.

Chen M, Zhao D Mol Pharm. 2024; 21(11):5413-5429.

PMID: 39373242 PMC: 11539062. DOI: 10.1021/acs.molpharmaceut.4c00563.

The role of mitochondria in tumor metastasis and advances in mitochondria-targeted cancer therapy.

Chen F, Xue Y, Zhang W, Zhou H, Zhou Z, Chen T Cancer Metastasis Rev. 2024; 43(4):1419-1443.

PMID: 39307891 PMC: 11554835. DOI: 10.1007/s10555-024-10211-9.

References

El Andaloussi S, Mager I, Breakefield X, Wood M . Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov. 2013; 12(5):347-57. DOI: 10.1038/nrd3978. View

Liotta L, Kohn E . The microenvironment of the tumour-host interface. Nature. 2001; 411(6835):375-9. DOI: 10.1038/35077241. View

Ishihara D, Dovas A, Hernandez L, Pozzuto M, Wyckoff J, Segall J . Wiskott-Aldrich syndrome protein regulates leukocyte-dependent breast cancer metastasis. Cell Rep. 2013; 4(3):429-36. PMC: 3777703. DOI: 10.1016/j.celrep.2013.07.007. View

Delage E, Cordero Cervantes D, Penard E, Schmitt C, Syan S, Disanza A . Differential identity of Filopodia and Tunneling Nanotubes revealed by the opposite functions of actin regulatory complexes. Sci Rep. 2016; 6:39632. PMC: 5180355. DOI: 10.1038/srep39632. View

Wang J, Cao Z, Zhang X, Nakamura M, Sun M, Hartman J . Novel mechanism of macrophage-mediated metastasis revealed in a zebrafish model of tumor development. Cancer Res. 2014; 75(2):306-15. DOI: 10.1158/0008-5472.CAN-14-2819. View

Dai J, Ma D, Zang S, Guo D, Qu X, Ye J . Cross-talk between Notch and EGFR signaling in human breast cancer cells. Cancer Invest. 2009; 27(5):533-40. DOI: 10.1080/07357900802563036. View

Francis K, Palsson B . Effective intercellular communication distances are determined by the relative time constants for cyto/chemokine secretion and diffusion. Proc Natl Acad Sci U S A. 1997; 94(23):12258-62. PMC: 24899. DOI: 10.1073/pnas.94.23.12258. View

Chaffer C, Weinberg R . A perspective on cancer cell metastasis. Science. 2011; 331(6024):1559-64. DOI: 10.1126/science.1203543. View

Xu W, Santini P, Sullivan J, He B, Shan M, Ball S . HIV-1 evades virus-specific IgG2 and IgA responses by targeting systemic and intestinal B cells via long-range intercellular conduits. Nat Immunol. 2009; 10(9):1008-17. PMC: 2784687. DOI: 10.1038/ni.1753. View

10.

Karagiannis G, Pastoriza J, Wang Y, Harney A, Entenberg D, Pignatelli J . Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mechanism. Sci Transl Med. 2017; 9(397). PMC: 5592784. DOI: 10.1126/scitranslmed.aan0026. View

11.

Rustom A, Saffrich R, Markovic I, Walther P, Gerdes H . Nanotubular highways for intercellular organelle transport. Science. 2004; 303(5660):1007-10. DOI: 10.1126/science.1093133. View

12.

Baker A, Zlobin A, Osipo C . Notch-EGFR/HER2 Bidirectional Crosstalk in Breast Cancer. Front Oncol. 2015; 4:360. PMC: 4264417. DOI: 10.3389/fonc.2014.00360. View

13.

Denning T, Wang Y, Patel S, Williams I, Pulendran B . Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses. Nat Immunol. 2007; 8(10):1086-94. DOI: 10.1038/ni1511. View

14.

Sparano J, Gray R, Oktay M, Entenberg D, Rohan T, Xue X . A metastasis biomarker (MetaSite ™ Score) is associated with distant recurrence in hormone receptor-positive, HER2-negative early-stage breast cancer. NPJ Breast Cancer. 2017; 3:42. PMC: 5678158. DOI: 10.1038/s41523-017-0043-5. View

15.

Pollard J . Macrophages define the invasive microenvironment in breast cancer. J Leukoc Biol. 2008; 84(3):623-30. PMC: 2516896. DOI: 10.1189/jlb.1107762. View

16.

Teng Y, Xie X, Walker S, White D, Mumm J, Cowell J . Evaluating human cancer cell metastasis in zebrafish. BMC Cancer. 2013; 13:453. PMC: 3852235. DOI: 10.1186/1471-2407-13-453. View

17.

Lou E, Zhai E, Sarkari A, Desir S, Wong P, Iizuka Y . Cellular and Molecular Networking Within the Ecosystem of Cancer Cell Communication via Tunneling Nanotubes. Front Cell Dev Biol. 2018; 6:95. PMC: 6176212. DOI: 10.3389/fcell.2018.00095. View

18.

Patsialou A, Bravo-Cordero J, Wang Y, Entenberg D, Liu H, Clarke M . Intravital multiphoton imaging reveals multicellular streaming as a crucial component of in vivo cell migration in human breast tumors. Intravital. 2014; 2(2):e25294. PMC: 3908591. DOI: 10.4161/intv.25294. View

19.

Yamaguchi H, Pixley F, Condeelis J . Invadopodia and podosomes in tumor invasion. Eur J Cell Biol. 2006; 85(3-4):213-8. DOI: 10.1016/j.ejcb.2005.10.004. View

20.

Sidani M, Wyckoff J, Xue C, Segall J, Condeelis J . Probing the microenvironment of mammary tumors using multiphoton microscopy. J Mammary Gland Biol Neoplasia. 2006; 11(2):151-63. DOI: 10.1007/s10911-006-9021-5. View