Tumor cell intravasation

Serena P H Chiang, Ramon M. Cabrera, Jeffrey E. Segall

Research output: Contribution to journalReview article

63 Citations (Scopus)

Abstract

The process of entering the bloodstream, intravasation, is a necessary step in the development of distant metastases. The focus of this review is on the pathways and molecules that have been identified as being important based on current in vitro and in vivo assays for intravasation. Properties of the vasculature which are important for intravasation include microvessel density and also diameter of the vasculature, with increased intravasation correlating with increased vessel diameter in some tumors. TGFB signaling can enhance intravasation at least in part through induction of EMT, and we discuss other TGFB target genes that are important for intravasation. In addition to TGFB signaling, a number of studies have demonstrated that activation of EGF receptor family members stimulates intravasation, with downstream signaling through PI3K, N-WASP, RhoA, and WASP to induce invadopodia. With respect to proteases, there is strong evidence for contributions by uPA/uPAR, while the roles of MMPs in intravasation may be more tumor specific. Other cells including macrophages, fibroblasts, neutrophils, and platelets can also play a role in enhancing tumor cell intravasation. The technology is now available to interrogate the expression patterns of circulating tumor cells, which will provide an important reality check for the model systems being used. With a better understanding of the mechanisms underlying intravasation, the goal is to provide new opportunities for improving prognosis as well as potentially developing new treatments.

Original languageEnglish (US)
Pages (from-to)C1-C14
JournalAmerican Journal of Physiology - Cell Physiology
Volume311
Issue number1
DOIs
StatePublished - Jul 1 2016

Fingerprint

Circulating Neoplastic Cells
Neoplasms
Microvessels
Matrix Metalloproteinases
Phosphatidylinositol 3-Kinases
Epidermal Growth Factor Receptor
Neutrophils
Peptide Hydrolases
Blood Platelets
Fibroblasts
Macrophages
Neoplasm Metastasis
Technology
Genes
In Vitro Techniques
Podosomes

Keywords

  • Angiogenesis
  • EGFR
  • Intravasation
  • Metastasis
  • TGFB
  • UPA

ASJC Scopus subject areas

  • Physiology
  • Medicine(all)
  • Cell Biology

Cite this

Tumor cell intravasation. / Chiang, Serena P H; Cabrera, Ramon M.; Segall, Jeffrey E.

In: American Journal of Physiology - Cell Physiology, Vol. 311, No. 1, 01.07.2016, p. C1-C14.

Research output: Contribution to journalReview article

Chiang, Serena P H ; Cabrera, Ramon M. ; Segall, Jeffrey E. / Tumor cell intravasation. In: American Journal of Physiology - Cell Physiology. 2016 ; Vol. 311, No. 1. pp. C1-C14.
@article{3a6858ec6a1347108e8360684ef905be,
title = "Tumor cell intravasation",
abstract = "The process of entering the bloodstream, intravasation, is a necessary step in the development of distant metastases. The focus of this review is on the pathways and molecules that have been identified as being important based on current in vitro and in vivo assays for intravasation. Properties of the vasculature which are important for intravasation include microvessel density and also diameter of the vasculature, with increased intravasation correlating with increased vessel diameter in some tumors. TGFB signaling can enhance intravasation at least in part through induction of EMT, and we discuss other TGFB target genes that are important for intravasation. In addition to TGFB signaling, a number of studies have demonstrated that activation of EGF receptor family members stimulates intravasation, with downstream signaling through PI3K, N-WASP, RhoA, and WASP to induce invadopodia. With respect to proteases, there is strong evidence for contributions by uPA/uPAR, while the roles of MMPs in intravasation may be more tumor specific. Other cells including macrophages, fibroblasts, neutrophils, and platelets can also play a role in enhancing tumor cell intravasation. The technology is now available to interrogate the expression patterns of circulating tumor cells, which will provide an important reality check for the model systems being used. With a better understanding of the mechanisms underlying intravasation, the goal is to provide new opportunities for improving prognosis as well as potentially developing new treatments.",
keywords = "Angiogenesis, EGFR, Intravasation, Metastasis, TGFB, UPA",
author = "Chiang, {Serena P H} and Cabrera, {Ramon M.} and Segall, {Jeffrey E.}",
year = "2016",
month = "7",
day = "1",
doi = "10.1152/ajpcell.00238.2015",
language = "English (US)",
volume = "311",
pages = "C1--C14",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "1",

}

TY - JOUR

T1 - Tumor cell intravasation

AU - Chiang, Serena P H

AU - Cabrera, Ramon M.

AU - Segall, Jeffrey E.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - The process of entering the bloodstream, intravasation, is a necessary step in the development of distant metastases. The focus of this review is on the pathways and molecules that have been identified as being important based on current in vitro and in vivo assays for intravasation. Properties of the vasculature which are important for intravasation include microvessel density and also diameter of the vasculature, with increased intravasation correlating with increased vessel diameter in some tumors. TGFB signaling can enhance intravasation at least in part through induction of EMT, and we discuss other TGFB target genes that are important for intravasation. In addition to TGFB signaling, a number of studies have demonstrated that activation of EGF receptor family members stimulates intravasation, with downstream signaling through PI3K, N-WASP, RhoA, and WASP to induce invadopodia. With respect to proteases, there is strong evidence for contributions by uPA/uPAR, while the roles of MMPs in intravasation may be more tumor specific. Other cells including macrophages, fibroblasts, neutrophils, and platelets can also play a role in enhancing tumor cell intravasation. The technology is now available to interrogate the expression patterns of circulating tumor cells, which will provide an important reality check for the model systems being used. With a better understanding of the mechanisms underlying intravasation, the goal is to provide new opportunities for improving prognosis as well as potentially developing new treatments.

AB - The process of entering the bloodstream, intravasation, is a necessary step in the development of distant metastases. The focus of this review is on the pathways and molecules that have been identified as being important based on current in vitro and in vivo assays for intravasation. Properties of the vasculature which are important for intravasation include microvessel density and also diameter of the vasculature, with increased intravasation correlating with increased vessel diameter in some tumors. TGFB signaling can enhance intravasation at least in part through induction of EMT, and we discuss other TGFB target genes that are important for intravasation. In addition to TGFB signaling, a number of studies have demonstrated that activation of EGF receptor family members stimulates intravasation, with downstream signaling through PI3K, N-WASP, RhoA, and WASP to induce invadopodia. With respect to proteases, there is strong evidence for contributions by uPA/uPAR, while the roles of MMPs in intravasation may be more tumor specific. Other cells including macrophages, fibroblasts, neutrophils, and platelets can also play a role in enhancing tumor cell intravasation. The technology is now available to interrogate the expression patterns of circulating tumor cells, which will provide an important reality check for the model systems being used. With a better understanding of the mechanisms underlying intravasation, the goal is to provide new opportunities for improving prognosis as well as potentially developing new treatments.

KW - Angiogenesis

KW - EGFR

KW - Intravasation

KW - Metastasis

KW - TGFB

KW - UPA

UR - http://www.scopus.com/inward/record.url?scp=84983598029&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84983598029&partnerID=8YFLogxK

U2 - 10.1152/ajpcell.00238.2015

DO - 10.1152/ajpcell.00238.2015

M3 - Review article

C2 - 27076614

AN - SCOPUS:84983598029

VL - 311

SP - C1-C14

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 1

ER -