Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis

Jacky G. Goetz; Susana Minguet; Inmaculada Navarro-Lérida; Juan José Lazcano; Rafael Samaniego; Enrique Calvo; Marta Tello; Teresa Osteso-Ibáñez; Teijo Pellinen; Asier Echarri; Ana Cerezo; Andrés J.P. Klein-Szanto; Ricardo Garcia; Patricia J. Keely; Paloma Sánchez-Mateos; Edna Cukierman; Miguel A. Del Pozo

doi:10.1016/j.cell.2011.05.040

Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis

Jacky G. Goetz, Susana Minguet, Inmaculada Navarro-Lérida, Juan José Lazcano, Rafael Samaniego, Enrique Calvo, Marta Tello, Teresa Osteso-Ibáñez, Teijo Pellinen, Asier Echarri, Ana Cerezo, Andrés J.P. Klein-Szanto, Ricardo Garcia, Patricia J. Keely, Paloma Sánchez-Mateos, Edna Cukierman, Miguel A. Del Pozo

Research output: Contribution to journal › Article › peer-review

608 Scopus citations

Abstract

Mechanotransduction is a key determinant of tissue homeostasis and tumor progression. It is driven by intercellular adhesions, cell contractility, and forces generated within the microenvironment and is dependent on extracellular matrix composition, organization, and compliance. We show that caveolin-1 (Cav1) favors cell elongation in three-dimensional cultures and promotes Rho- and force-dependent contraction, matrix alignment, and microenvironment stiffening through regulation of p190RhoGAP. In turn, microenvironment remodeling by Cav1 fibroblasts forces cell elongation. Cav1-deficient mice have disorganized stromal tissue architecture. Stroma associated with human carcinomas and melanoma metastases is enriched in Cav1-expressing carcinoma-associated fibroblasts (CAFs). Cav1 expression in breast CAFs correlates with low survival, and Cav1 depletion in CAFs decreases CAF contractility. Consistently, fibroblast expression of Cav1, through p190RhoGAP regulation, favors directional migration and invasiveness of carcinoma cells in vitro. In vivo, stromal Cav1 remodels peri- and intratumoral microenvironments to facilitate tumor invasion, correlating with increased metastatic potency. Thus, Cav1 modulates tissue responses through force-dependent architectural regulation of the microenvironment. PaperFlick:

Original language	English
Pages (from-to)	148-163
Number of pages	16
Journal	Cell
Volume	146
Issue number	1
DOIs	https://doi.org/10.1016/j.cell.2011.05.040
State	Published - Jul 8 2011

Keywords

Animals
Caveolin 1/metabolism
Cell Movement
Fibroblasts/pathology
Humans
Melanoma/pathology
Mice
Mice, Knockout
Neoplasm Metastasis/pathology
Neoplasms/pathology

Access to Document

10.1016/j.cell.2011.05.040

Cite this

Goetz, J. G., Minguet, S., Navarro-Lérida, I., Lazcano, J. J., Samaniego, R., Calvo, E., Tello, M., Osteso-Ibáñez, T., Pellinen, T., Echarri, A., Cerezo, A., Klein-Szanto, A. J. P., Garcia, R., Keely, P. J., Sánchez-Mateos, P., Cukierman, E., & Del Pozo, M. A. (2011). Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis. Cell, 146(1), 148-163. https://doi.org/10.1016/j.cell.2011.05.040

@article{1e958081f4e944ddab7cb7aa1a3c07d1,

title = "Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis",

abstract = "Mechanotransduction is a key determinant of tissue homeostasis and tumor progression. It is driven by intercellular adhesions, cell contractility, and forces generated within the microenvironment and is dependent on extracellular matrix composition, organization, and compliance. We show that caveolin-1 (Cav1) favors cell elongation in three-dimensional cultures and promotes Rho- and force-dependent contraction, matrix alignment, and microenvironment stiffening through regulation of p190RhoGAP. In turn, microenvironment remodeling by Cav1 fibroblasts forces cell elongation. Cav1-deficient mice have disorganized stromal tissue architecture. Stroma associated with human carcinomas and melanoma metastases is enriched in Cav1-expressing carcinoma-associated fibroblasts (CAFs). Cav1 expression in breast CAFs correlates with low survival, and Cav1 depletion in CAFs decreases CAF contractility. Consistently, fibroblast expression of Cav1, through p190RhoGAP regulation, favors directional migration and invasiveness of carcinoma cells in vitro. In vivo, stromal Cav1 remodels peri- and intratumoral microenvironments to facilitate tumor invasion, correlating with increased metastatic potency. Thus, Cav1 modulates tissue responses through force-dependent architectural regulation of the microenvironment. PaperFlick:",

keywords = "Animals, Caveolin 1/metabolism, Cell Movement, Fibroblasts/pathology, Humans, Melanoma/pathology, Mice, Mice, Knockout, Neoplasm Metastasis/pathology, Neoplasms/pathology",

author = "Goetz, {Jacky G.} and Susana Minguet and Inmaculada Navarro-L{\'e}rida and Lazcano, {Juan Jos{\'e}} and Rafael Samaniego and Enrique Calvo and Marta Tello and Teresa Osteso-Ib{\'a}{\~n}ez and Teijo Pellinen and Asier Echarri and Ana Cerezo and Klein-Szanto, {Andr{\'e}s J.P.} and Ricardo Garcia and Keely, {Patricia J.} and Paloma S{\'a}nchez-Mateos and Edna Cukierman and {Del Pozo}, {Miguel A.}",

year = "2011",

month = jul,

day = "8",

doi = "10.1016/j.cell.2011.05.040",

language = "English",

volume = "146",

pages = "148--163",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "1",

}

Goetz, JG, Minguet, S, Navarro-Lérida, I, Lazcano, JJ, Samaniego, R, Calvo, E, Tello, M, Osteso-Ibáñez, T, Pellinen, T, Echarri, A, Cerezo, A, Klein-Szanto, AJP, Garcia, R, Keely, PJ, Sánchez-Mateos, P, Cukierman, E & Del Pozo, MA 2011, 'Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis', Cell, vol. 146, no. 1, pp. 148-163. https://doi.org/10.1016/j.cell.2011.05.040

TY - JOUR

T1 - Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis

AU - Goetz, Jacky G.

AU - Minguet, Susana

AU - Navarro-Lérida, Inmaculada

AU - Lazcano, Juan José

AU - Samaniego, Rafael

AU - Calvo, Enrique

AU - Tello, Marta

AU - Osteso-Ibáñez, Teresa

AU - Pellinen, Teijo

AU - Echarri, Asier

AU - Cerezo, Ana

AU - Klein-Szanto, Andrés J.P.

AU - Garcia, Ricardo

AU - Keely, Patricia J.

AU - Sánchez-Mateos, Paloma

AU - Cukierman, Edna

AU - Del Pozo, Miguel A.

PY - 2011/7/8

Y1 - 2011/7/8

N2 - Mechanotransduction is a key determinant of tissue homeostasis and tumor progression. It is driven by intercellular adhesions, cell contractility, and forces generated within the microenvironment and is dependent on extracellular matrix composition, organization, and compliance. We show that caveolin-1 (Cav1) favors cell elongation in three-dimensional cultures and promotes Rho- and force-dependent contraction, matrix alignment, and microenvironment stiffening through regulation of p190RhoGAP. In turn, microenvironment remodeling by Cav1 fibroblasts forces cell elongation. Cav1-deficient mice have disorganized stromal tissue architecture. Stroma associated with human carcinomas and melanoma metastases is enriched in Cav1-expressing carcinoma-associated fibroblasts (CAFs). Cav1 expression in breast CAFs correlates with low survival, and Cav1 depletion in CAFs decreases CAF contractility. Consistently, fibroblast expression of Cav1, through p190RhoGAP regulation, favors directional migration and invasiveness of carcinoma cells in vitro. In vivo, stromal Cav1 remodels peri- and intratumoral microenvironments to facilitate tumor invasion, correlating with increased metastatic potency. Thus, Cav1 modulates tissue responses through force-dependent architectural regulation of the microenvironment. PaperFlick:

AB - Mechanotransduction is a key determinant of tissue homeostasis and tumor progression. It is driven by intercellular adhesions, cell contractility, and forces generated within the microenvironment and is dependent on extracellular matrix composition, organization, and compliance. We show that caveolin-1 (Cav1) favors cell elongation in three-dimensional cultures and promotes Rho- and force-dependent contraction, matrix alignment, and microenvironment stiffening through regulation of p190RhoGAP. In turn, microenvironment remodeling by Cav1 fibroblasts forces cell elongation. Cav1-deficient mice have disorganized stromal tissue architecture. Stroma associated with human carcinomas and melanoma metastases is enriched in Cav1-expressing carcinoma-associated fibroblasts (CAFs). Cav1 expression in breast CAFs correlates with low survival, and Cav1 depletion in CAFs decreases CAF contractility. Consistently, fibroblast expression of Cav1, through p190RhoGAP regulation, favors directional migration and invasiveness of carcinoma cells in vitro. In vivo, stromal Cav1 remodels peri- and intratumoral microenvironments to facilitate tumor invasion, correlating with increased metastatic potency. Thus, Cav1 modulates tissue responses through force-dependent architectural regulation of the microenvironment. PaperFlick:

KW - Animals

KW - Caveolin 1/metabolism

KW - Cell Movement

KW - Fibroblasts/pathology

KW - Humans

KW - Melanoma/pathology

KW - Mice

KW - Mice, Knockout

KW - Neoplasm Metastasis/pathology

KW - Neoplasms/pathology

UR - http://www.scopus.com/inward/record.url?scp=79959947008&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2011.05.040

DO - 10.1016/j.cell.2011.05.040

M3 - Article

C2 - 21729786

SN - 0092-8674

VL - 146

SP - 148

EP - 163

JO - Cell

JF - Cell

IS - 1

ER -

Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this