Stroma in normal and cancer wound healing

It is currently believed that stroma, the connective framework of biological tissues, plays a central role in normal wound healing and in cancer. In both these contexts, stromal cellular components such as activated fibroblasts interact with complex protein networks that include growth factors, stru...

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Published in:	The FEBS journal Vol. 286; no. 15; pp. 2909 - 2920
Main Authors:	Huet, Eric, Jaroz, Camille, Nguyen, Hoang Quy, Belkacemi, Yazid, Taille, Alexandre, Stavrinides, Vasilis, Whitaker, Hayley
Format:	Journal Article
Language:	English
Published:	England Blackwell Publishing Ltd 01.08.2019
Subjects:	Animals Cancer cancer‐associated fibroblasts Cell proliferation Cellular communication Connective Tissue - metabolism Connective Tissue - pathology Connective Tissue - radiation effects Crosstalk EMMPRIN Extracellular Matrix Proteins - genetics Extracellular Matrix Proteins - metabolism FAPα Fibroblasts fibrosis Growth factors Humans Metastases metastasis myofibroblasts neoplasm cells neoplasms Neoplasms - metabolism Neoplasms - radiotherapy proteinases Proteins Radiation Injuries - etiology Radiation Injuries - metabolism Radiation therapy radiotherapy Radiotherapy - adverse effects Signal Transduction structural proteins TGFβ Therapeutic applications tissue repair Tissues tumour microenvironment Wound Healing cancer-associated fibroblasts fibroblasts wound healing TGFβ radiotherapy EMMPRIN fibrosis tumour microenvironment FAPα myofibroblasts
ISSN:	1742-464X, 1742-4658, 1742-4658
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Abstract	It is currently believed that stroma, the connective framework of biological tissues, plays a central role in normal wound healing and in cancer. In both these contexts, stromal cellular components such as activated fibroblasts interact with complex protein networks that include growth factors, structural protein or proteinases in order to initiate and sustain an extensive remodelling process. However, although this process is usually spatially and temporally self‐limited, it is unregulated in the case of cancer and leads to uncontrolled cell proliferation and invasion within tissues, metastasis and therapeutic resistance. In this review, we outline the role of stroma in normal healing, cancer and post radiotherapy, with a particular focus on the crosstalk between normal or cancer cells and fibroblasts. Understanding these mechanisms is particularly important as several stromal components have been proposed as potential therapeutic targets. Stromal modification, a key step in the control of wound healing, tumour progression and radiation‐induced fibrosis, is characterized by the differentiation of quiescent fibroblasts into an activated state, which results in crosstalk among fibroblasts and normal or cancer cells. Understanding these activation mechanisms, which involve extracellular matrix metalloproteinase inducer and transforming growth factor beta, is important because several stromal components are potential therapeutic targets.
AbstractList	It is currently believed that stroma, the connective framework of biological tissues, plays a central role in normal wound healing and in cancer. In both these contexts, stromal cellular components such as activated fibroblasts interact with complex protein networks that include growth factors, structural protein or proteinases in order to initiate and sustain an extensive remodelling process. However, although this process is usually spatially and temporally self‐limited, it is unregulated in the case of cancer and leads to uncontrolled cell proliferation and invasion within tissues, metastasis and therapeutic resistance. In this review, we outline the role of stroma in normal healing, cancer and post radiotherapy, with a particular focus on the crosstalk between normal or cancer cells and fibroblasts. Understanding these mechanisms is particularly important as several stromal components have been proposed as potential therapeutic targets. It is currently believed that stroma, the connective framework of biological tissues, plays a central role in normal wound healing and in cancer. In both these contexts, stromal cellular components such as activated fibroblasts interact with complex protein networks that include growth factors, structural protein or proteinases in order to initiate and sustain an extensive remodelling process. However, although this process is usually spatially and temporally self‐limited, it is unregulated in the case of cancer and leads to uncontrolled cell proliferation and invasion within tissues, metastasis and therapeutic resistance. In this review, we outline the role of stroma in normal healing, cancer and post radiotherapy, with a particular focus on the crosstalk between normal or cancer cells and fibroblasts. Understanding these mechanisms is particularly important as several stromal components have been proposed as potential therapeutic targets. Stromal modification, a key step in the control of wound healing, tumour progression and radiation‐induced fibrosis, is characterized by the differentiation of quiescent fibroblasts into an activated state, which results in crosstalk among fibroblasts and normal or cancer cells. Understanding these activation mechanisms, which involve extracellular matrix metalloproteinase inducer and transforming growth factor beta, is important because several stromal components are potential therapeutic targets. It is currently believed that stroma, the connective framework of biological tissues, plays a central role in normal wound healing and in cancer. In both these contexts, stromal cellular components such as activated fibroblasts interact with complex protein networks that include growth factors, structural protein or proteinases in order to initiate and sustain an extensive remodelling process. However, although this process is usually spatially and temporally self-limited, it is unregulated in the case of cancer and leads to uncontrolled cell proliferation and invasion within tissues, metastasis and therapeutic resistance. In this review, we outline the role of stroma in normal healing, cancer and post radiotherapy, with a particular focus on the crosstalk between normal or cancer cells and fibroblasts. Understanding these mechanisms is particularly important as several stromal components have been proposed as potential therapeutic targets.It is currently believed that stroma, the connective framework of biological tissues, plays a central role in normal wound healing and in cancer. In both these contexts, stromal cellular components such as activated fibroblasts interact with complex protein networks that include growth factors, structural protein or proteinases in order to initiate and sustain an extensive remodelling process. However, although this process is usually spatially and temporally self-limited, it is unregulated in the case of cancer and leads to uncontrolled cell proliferation and invasion within tissues, metastasis and therapeutic resistance. In this review, we outline the role of stroma in normal healing, cancer and post radiotherapy, with a particular focus on the crosstalk between normal or cancer cells and fibroblasts. Understanding these mechanisms is particularly important as several stromal components have been proposed as potential therapeutic targets.
Author	Taille, Alexandre Stavrinides, Vasilis Nguyen, Hoang Quy Huet, Eric Belkacemi, Yazid Jaroz, Camille Whitaker, Hayley
Author_xml	– sequence: 1 givenname: Eric surname: Huet fullname: Huet, Eric email: huet@u-pec.fr organization: University College London – sequence: 2 givenname: Camille surname: Jaroz fullname: Jaroz, Camille organization: Université Paris‐Est, UPEC – sequence: 3 givenname: Hoang Quy surname: Nguyen fullname: Nguyen, Hoang Quy organization: INSERM, U955, Equipe 7 – sequence: 4 givenname: Yazid surname: Belkacemi fullname: Belkacemi, Yazid organization: Service d'oncologie‐radiothérapie et Centre Sein Henri Mondor Créteil – sequence: 5 givenname: Alexandre surname: Taille fullname: Taille, Alexandre organization: Service d'urologie – sequence: 6 givenname: Vasilis surname: Stavrinides fullname: Stavrinides, Vasilis organization: University College London – sequence: 7 givenname: Hayley surname: Whitaker fullname: Whitaker, Hayley organization: University College London
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Keywords	cancer-associated fibroblasts fibroblasts wound healing TGFβ radiotherapy EMMPRIN fibrosis tumour microenvironment FAPα myofibroblasts
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Snippet	It is currently believed that stroma, the connective framework of biological tissues, plays a central role in normal wound healing and in cancer. In both these...
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SubjectTerms	Animals Cancer cancer‐associated fibroblasts Cell proliferation Cellular communication Connective Tissue - metabolism Connective Tissue - pathology Connective Tissue - radiation effects Crosstalk EMMPRIN Extracellular Matrix Proteins - genetics Extracellular Matrix Proteins - metabolism FAPα Fibroblasts fibrosis Growth factors Humans Metastases metastasis myofibroblasts neoplasm cells neoplasms Neoplasms - metabolism Neoplasms - radiotherapy proteinases Proteins Radiation Injuries - etiology Radiation Injuries - metabolism Radiation therapy radiotherapy Radiotherapy - adverse effects Signal Transduction structural proteins TGFβ Therapeutic applications tissue repair Tissues tumour microenvironment Wound Healing
Title	Stroma in normal and cancer wound healing
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