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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.
PMID
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Authors

Mayor MeshTerms
Keywords

EGFR

animal models of cancer

cancer metastasis

cell intravasation

chorioallantoic membrane model

mouse ear tumor model

stromal invasion

tumor angiogenesis

tumor cell migration

tumor invasion

Journal Title cell reports
Publication Year Start




PMID- 28423322
OWN - NLM
STAT- In-Process
DA  - 20170419
LR  - 20170419
IS  - 2211-1247 (Electronic)
VI  - 19
IP  - 3
DP  - 2017 Apr 18
TI  - Intratumoral Cancer Cell Intravasation Can Occur Independent of Invasion into the
      Adjacent Stroma.
PG  - 601-616
LID - S2211-1247(17)30425-4 [pii]
LID - 10.1016/j.celrep.2017.03.064 [doi]
AB  - 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.
CI  - Copyright (c) 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Deryugina, Elena I
AU  - Deryugina EI
AD  - Department of Molecular Medicine, The Scripps Research Institute, 10550 North
      Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address:
      [email protected]
FAU - Kiosses, William B
AU  - Kiosses WB
AD  - Confocal Microscopy Core Facility, The Scripps Research Institute, 10550 North
      Torrey Pines Road, La Jolla, CA 92037, USA.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
OTO - NOTNLM
OT  - EGFR
OT  - animal models of cancer
OT  - cancer metastasis
OT  - cell intravasation
OT  - chorioallantoic membrane model
OT  - mouse ear tumor model
OT  - stromal invasion
OT  - tumor angiogenesis
OT  - tumor cell migration
OT  - tumor invasion
EDAT- 2017/04/20 06:00
MHDA- 2017/04/20 06:00
CRDT- 2017/04/20 06:00
PHST- 2016/08/18 [received]
PHST- 2017/01/29 [revised]
PHST- 2017/03/21 [accepted]
AID - S2211-1247(17)30425-4 [pii]
AID - 10.1016/j.celrep.2017.03.064 [doi]
PST - ppublish
SO  - Cell Rep. 2017 Apr 18;19(3):601-616. doi: 10.1016/j.celrep.2017.03.064.

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