Tumor-stroma biomechanical crosstalk: a perspective on the role of caveolin-1 in tumor progression
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Tumor-stroma biomechanical crosstalk: a perspective on the role of caveolin-1 in tumor progression Fidel Nicolás Lolo 1 & Víctor Jiménez-Jiménez 1 & Miguel Sánchez-Álvarez 1 & Miguel Ángel del Pozo 1
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Tumor stiffening is a hallmark of malignancy that actively drives tumor progression and aggressiveness. Recent research has shed light onto several molecular underpinnings of this biomechanical process, which has a reciprocal crosstalk between tumor cells, stromal fibroblasts, and extracellular matrix remodeling at its core. This dynamic communication shapes the tumor microenvironment; significantly determines disease features including therapeutic resistance, relapse, or metastasis; and potentially holds the key for novel antitumor strategies. Caveolae and their components emerge as integrators of different aspects of cell function, mechanotransduction, and ECM–cell interaction. Here, we review our current knowledge on the several pivotal roles of the essential caveolar component caveolin-1 in this multidirectional biomechanical crosstalk and highlight standing questions in the field. Keywords Mechanobiology . Caveolae . Caveolin-1 . Cancer . Stromal remodeling . Extracellular matrix (ECM) . Cancer-associated fibroblasts (CAFs) . YAP/TAZ . Integrin signaling . Cell contraction . Tumor cell reprogramming . Metastasis
1 Introduction When describing alterations indicative of tissue insult and inflammation, the roman encyclopedist Celsus (c. 25 BC–c. 50 AD) included “tumor” (swelling and stiffening; along with calor (warmth), rubor (redness), and dolor (pain)) as one of its cardinal signs. Ever since, and especially for the case of abnormal mass growth, swelling and stiffness have constituted an important diagnostic and prognostic parameter in classical medicine. The existence of links between stiffening and tumor progression was early demonstrated when studying the relevance of interstitial fluid pressure in an experimental rabbit model of epithelial carcinoma [1]. Subsequent studies corroborated that tumors exhibit differential, measurable mechanical features, and these correlate with aggressiveness and tumor progression (reviewed in [2–4]). Indeed, mechanical forces profoundly influence cell function regarding not only their Fidel Nicolás Lolo, Víctor Jiménez-Jiménez and Miguel SánchezÁlvarez contributed equally to this work. * Miguel Ángel del Pozo [email protected] 1
Mechanoadaptation and Caveolae Biology Lab, Cell and Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
motility but also their differentiation state and proliferation [5–7], and mechanical properties of tumors affect their progression, vascularization, drug delivery, and therapeutic resistance and propensity to metastasize [8–13]. Enabled by emerging technologies, the systematic study of tumor biomechanics across scales has soared in recent years, and their intervention is intensely explored as a potential opportunity to
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