In:
Molecular Biology of the Cell, American Society for Cell Biology (ASCB), Vol. 31, No. 12 ( 2020-06-01), p. 1259-1272
Abstract:
Actin-based tubular connections between cells have been observed in many cell types. Termed “tunneling nanotubes (TNTs),” “membrane nanotubes,” “tumor microtubes (TMTs),” or “cytonemes,” these protrusions interconnect cells in dynamic networks. Structural features in these protrusions vary between cellular systems, including tubule diameter and the presence of microtubules. We find tubular protrusions, which we classify as TMTs, in a pancreatic cancer cell line, Dartmouth-Hitchcock Pancreatic Cancer (DHPC)-018. TMTs are present in DHPC–018-derived tumors in mice, as well as in a mouse model of pancreatic cancer and a subset of primary human tumors. DHPC-018 TMTs have heterogeneous diameter (0.39–5.85 µm, median 1.92 µm) and contain actin filaments, microtubules, and cytokeratin 19-based intermediate filaments. TMTs do not allow intercellular transfer of cytoplasmic GFP. Actin filaments are cortical within the protrusion, as opposed to TNTs, in which filaments run down the center. TMTs are dynamic in length, but are long lived (median 〉 60 min). Inhibition of actin polymerization, but not microtubules, results in TMT loss. Extracellular calcium is necessary for TMT maintenance. A second class of tubular protrusion, which we term cell-substrate protrusion, has similar width range and cytoskeletal features but makes contact with the substratum as opposed to another cell. Similar to previous work on TNTs, we find two assembly mechanisms for TMTs, which we term “pull-away” and “search-and-capture.” Inhibition of Arp2/3 complex inhibits TMT assembly by both mechanisms. This work demonstrates that the actin architecture of TMTs in pancreatic cancer cells is fundamentally different from that of TNTs and demonstrates the role of Arp2/3 complex in TMT assembly.
Type of Medium:
Online Resource
ISSN:
1059-1524
,
1939-4586
DOI:
10.1091/mbc.E19-11-0605
Language:
English
Publisher:
American Society for Cell Biology (ASCB)
Publication Date:
2020
detail.hit.zdb_id:
1474922-1
SSG:
12
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