PreprintArticleVersion 2Preserved in Portico This version is not peer-reviewed
A Model for the Dissemination of Circulating Tumour Cell Clusters Involving Platelet Recruitment and a Plastic Switch between Cooperative and Individual Behaviours
Version 1
: Received: 2 October 2022 / Approved: 5 October 2022 / Online: 5 October 2022 (16:35:01 CEST)
Version 2
: Received: 18 July 2023 / Approved: 18 July 2023 / Online: 19 July 2023 (02:38:28 CEST)
Hapeman, J.D.; Carneiro, C.S.; Nedelcu, A.M. A Model for the Dissemination of Circulating Tumour Cell Clusters Involving Platelet Recruitment and a Plastic Switch between Cooperative and Individual Behaviours. BMC Ecology and Evolution 2023, 23, doi:10.1186/s12862-023-02147-5.
Hapeman, J.D.; Carneiro, C.S.; Nedelcu, A.M. A Model for the Dissemination of Circulating Tumour Cell Clusters Involving Platelet Recruitment and a Plastic Switch between Cooperative and Individual Behaviours. BMC Ecology and Evolution 2023, 23, doi:10.1186/s12862-023-02147-5.
Hapeman, J.D.; Carneiro, C.S.; Nedelcu, A.M. A Model for the Dissemination of Circulating Tumour Cell Clusters Involving Platelet Recruitment and a Plastic Switch between Cooperative and Individual Behaviours. BMC Ecology and Evolution 2023, 23, doi:10.1186/s12862-023-02147-5.
Hapeman, J.D.; Carneiro, C.S.; Nedelcu, A.M. A Model for the Dissemination of Circulating Tumour Cell Clusters Involving Platelet Recruitment and a Plastic Switch between Cooperative and Individual Behaviours. BMC Ecology and Evolution 2023, 23, doi:10.1186/s12862-023-02147-5.
Abstract
Background: As cancer progresses, cells acquire traits that allow them to disperse and disseminate to distant locations in the body – a process known as metastasis. While in the vasculature, these cells are referred to as circulating tumour cells (CTCs) and can manifest either as single cells or clusters of cells (i.e., CTC clusters), with the latter being the most aggressive. The increased metastatic potential of CTC clusters is generally associated with cooperative group benefits in terms of survival, such as increased resistance to shear stress, anoikis, immune attacks and drugs. However, the adoption of a group phenotype poses a challenge when exiting the vasculature (extravasation) as the large size can hinder the passage through vessel walls. Despite their significant role in the metastatic process, the mechanisms through which CTC clusters extravasate remain largely unknown. Based on the observed in vivo association between CTC clusters and platelets, we hypothesized that cancer cells take advantage of the platelet-derived Transforming Growth Factor Beta 1 (TGF-β1) – a signalling factor that has been widely implicated in many aspects of cancer, to facilitate their own dissemination. To address this possibility, we evaluated the effect of exogenous TGF-β1 on an experimentally evolved non-small lung cancer cell line that we previously developed and used to investigate the biology of CTC clusters. Results: We found that exogenous TGF-β1 induced the dissociation of clusters into adherent single cells. Once adhered, cells released their own TGF-β1 and were able to individually migrate and invade in the absence of exogenous TGF-β1. Based on these findings we developed a model that involves a TGF-β1-mediated plastic switch between a cooperative phenotype and a single-celled stage that enables the extravasation of CTC clusters. Conclusions: This model allows for the possibility that therapies can be developed against TGF-β1 signalling components and/or TGF-β1 target genes to suppress the metastatic potential of CTC clusters. Considering the negative impact that metastasis has on cancer prognosis and the lack of therapies against this process, interfering with the ability of CTC clusters to switch between cooperative and individual behaviours could provide new strategies to improve patient survival.
Biology and Life Sciences, Cell and Developmental Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Commenter: Jorian Hapeman
Commenter's Conflict of Interests: Author