Diversity in cancer invasion phenotypes indicates specific stroma regulated programs.
Cancer-stroma interaction
Collective invasion
Stromal invasion
Journal
Human cell
ISSN: 1749-0774
Titre abrégé: Hum Cell
Pays: Japan
ID NLM: 8912329
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
03
07
2020
accepted:
03
09
2020
pubmed:
17
9
2020
medline:
2
7
2021
entrez:
16
9
2020
Statut:
ppublish
Résumé
Tumor dissemination into the surrounding stroma is the initial step in a metastatic cascade. Invasion into stroma is a non-autonomous process for cancer, and its progression depends upon the stage of cancer, as well as the cells residing in the stroma. However, a systems framework to understand how stromal fibroblasts resist, collude, or aid cancer invasion has been lacking, limiting our understanding of the role of stromal biology in cancer metastasis. We and others have shown that gene perturbation in stromal fibroblasts can modulate cancer invasion into the stroma, highlighting the active role stroma plays in regulating its own invasion. However, cancer invasion into stroma is a complex higher-order process and consists of various sub-phenotypes that together can result in an invasion. Stromal invasion exhibits a diversity of modalities in vivo. It is not well understood if these diverse modalities are correlated, or they emanate from distinct mechanisms and if stromal biology could regulate these characteristics. These characteristics include the extent of invasion, formation, and persistence of invasive forks by cancer as opposed to a collective frontal invasion, the persistence of invading velocity by leader cells at the tip of invasive forks, etc. We posit that quantifying distinct aspects of collective invasion can provide useful suggestions about the plausible mechanisms regulating these processes, including whether the process is regulated by mechanics or by intercellular communication between stromal cells and cancer. Here, we have identified the sub-characteristics of invasion, which might be indicative of broader mechanisms regulating these processes, developed methods to quantify these metrics, and demonstrated that perturbation of stromal genes can modulate distinct aspects of collective invasion. Our results highlight that the genetic state of stromal fibroblasts can regulate complex phenomena involved in cancer dissemination and suggest that collective cancer invasion into stroma is an outcome of the complex interplay between cancer and stromal fibroblasts.
Identifiants
pubmed: 32935295
doi: 10.1007/s13577-020-00427-6
pii: 10.1007/s13577-020-00427-6
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
111-121Subventions
Organisme : NCI NIH HHS
ID : U54 CA209992
Pays : United States
Organisme : NCI NIH HHS
ID : IH RPPR 5U54CA209992
Pays : United States
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