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Intratumoral Cancer Cell Intravasation Can Occur Independent of Invasion into the Adjacent Stroma.


ABSTRACT: Intravasation, active entry of cancer cells into the circulation, is often considered to be a relatively late event in tumor development occurring after stromal invasion. Here, we provide evidence that intravasation can be initiated early during tumor development and proceed in parallel to or independent of tumor invasion into surrounding stroma. By applying direct and unbiased intravasation-scoring methods to two histologically distinct human cancer types in live-animal models, we demonstrate that intravasation takes place almost exclusively within the tumor core, involves intratumoral vasculature, and does not involve vasculotropic cancer cells invading tumor-adjacent stroma and migrating along tumor-converging blood vessels. Highlighting an additional role for EGFR in cancer, we find that EGFR is required for the development of an intravasation-sustaining intratumoral vasculature. Intratumoral localization of intravasation supports the notion that overt metastases in cancer patients could be initiated much earlier during cancer progression than appreciated within conventional clinical tumor staging systems.

SUBMITTER: Deryugina EI 

PROVIDER: S-EPMC5659755 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Intratumoral Cancer Cell Intravasation Can Occur Independent of Invasion into the Adjacent Stroma.

Deryugina Elena I EI   Kiosses William B WB  

Cell reports 20170401 3


Intravasation, active entry of cancer cells into the circulation, is often considered to be a relatively late event in tumor development occurring after stromal invasion. Here, we provide evidence that intravasation can be initiated early during tumor development and proceed in parallel to or independent of tumor invasion into surrounding stroma. By applying direct and unbiased intravasation-scoring methods to two histologically distinct human cancer types in live-animal models, we demonstrate t  ...[more]

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