Collective directional migration drives the formation of heteroclonal cancer cell clusters
Metastasisation occurs through the acquisition of invasive and survival capabilities that allow tumour cells to colonise distant sites. While the role of multicellular aggregates in cancer dissemination is acknowledged, the mechanisms that drive the formation of multiclonal cell aggregates are not f...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-09-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.13369 |
| _version_ | 1827822770047680512 |
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| author | Miriam Palmiero Isabel Cantarosso Laura diBlasio Valentina Monica Barbara Peracino Luca Primo Alberto Puliafito |
| author_facet | Miriam Palmiero Isabel Cantarosso Laura diBlasio Valentina Monica Barbara Peracino Luca Primo Alberto Puliafito |
| author_sort | Miriam Palmiero |
| collection | DOAJ |
| description | Metastasisation occurs through the acquisition of invasive and survival capabilities that allow tumour cells to colonise distant sites. While the role of multicellular aggregates in cancer dissemination is acknowledged, the mechanisms that drive the formation of multiclonal cell aggregates are not fully elucidated. Here, we show that cancer cells of different tissue of origins can perform collective directional migration and can actively form heteroclonal aggregates in 3D, through a proliferation‐independent mechanism. Coalescence of distant cell clusters is mediated by subcellular actin‐rich protrusions and multicellular outgrowths that extend towards neighbouring aggregates. Coherently, perturbation of cytoskeletal dynamics impairs collective migration while myosin II activation is necessary for multicellular movements. We put forward the hypothesis that cluster attraction is mediated by secreted soluble factors. Such a hypothesis is consistent with the abrogation of aggregation by inhibition of PI3K/AKT/mTOR and MEK/ERK, the chemoattracting activity of conditioned culture media and with a wide screening of secreted proteins. Our results present a novel collective migration model and shed light on the mechanisms of formation of heteroclonal aggregates in cancer. |
| first_indexed | 2024-03-12T02:02:21Z |
| format | Article |
| id | doaj.art-95b1bf163b2f42398d365bf5291aad6a |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-03-12T02:02:21Z |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-95b1bf163b2f42398d365bf5291aad6a2023-09-07T10:57:03ZengWileyMolecular Oncology1574-78911878-02612023-09-011791699172510.1002/1878-0261.13369Collective directional migration drives the formation of heteroclonal cancer cell clustersMiriam Palmiero0Isabel Cantarosso1Laura diBlasio2Valentina Monica3Barbara Peracino4Luca Primo5Alberto Puliafito6Candiolo Cancer Institute, FPO – IRCCS Candiolo ItalyCandiolo Cancer Institute, FPO – IRCCS Candiolo ItalyCandiolo Cancer Institute, FPO – IRCCS Candiolo ItalyCandiolo Cancer Institute, FPO – IRCCS Candiolo ItalyDepartment of Clinical and Biological Sciences San Luigi Hospital, University of Turin Orbassano ItalyCandiolo Cancer Institute, FPO – IRCCS Candiolo ItalyCandiolo Cancer Institute, FPO – IRCCS Candiolo ItalyMetastasisation occurs through the acquisition of invasive and survival capabilities that allow tumour cells to colonise distant sites. While the role of multicellular aggregates in cancer dissemination is acknowledged, the mechanisms that drive the formation of multiclonal cell aggregates are not fully elucidated. Here, we show that cancer cells of different tissue of origins can perform collective directional migration and can actively form heteroclonal aggregates in 3D, through a proliferation‐independent mechanism. Coalescence of distant cell clusters is mediated by subcellular actin‐rich protrusions and multicellular outgrowths that extend towards neighbouring aggregates. Coherently, perturbation of cytoskeletal dynamics impairs collective migration while myosin II activation is necessary for multicellular movements. We put forward the hypothesis that cluster attraction is mediated by secreted soluble factors. Such a hypothesis is consistent with the abrogation of aggregation by inhibition of PI3K/AKT/mTOR and MEK/ERK, the chemoattracting activity of conditioned culture media and with a wide screening of secreted proteins. Our results present a novel collective migration model and shed light on the mechanisms of formation of heteroclonal aggregates in cancer.https://doi.org/10.1002/1878-0261.133693D modelscollective migrationdirectional migrationheterogeneityimagingprotrusions |
| spellingShingle | Miriam Palmiero Isabel Cantarosso Laura diBlasio Valentina Monica Barbara Peracino Luca Primo Alberto Puliafito Collective directional migration drives the formation of heteroclonal cancer cell clusters Molecular Oncology 3D models collective migration directional migration heterogeneity imaging protrusions |
| title | Collective directional migration drives the formation of heteroclonal cancer cell clusters |
| title_full | Collective directional migration drives the formation of heteroclonal cancer cell clusters |
| title_fullStr | Collective directional migration drives the formation of heteroclonal cancer cell clusters |
| title_full_unstemmed | Collective directional migration drives the formation of heteroclonal cancer cell clusters |
| title_short | Collective directional migration drives the formation of heteroclonal cancer cell clusters |
| title_sort | collective directional migration drives the formation of heteroclonal cancer cell clusters |
| topic | 3D models collective migration directional migration heterogeneity imaging protrusions |
| url | https://doi.org/10.1002/1878-0261.13369 |
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