Unraveling the interplay between senescent dermal fibroblasts and cutaneous squamous cell carcinoma cell lines at different stages of tumorigenesis

Research output: Contribution to journalArticle

Abstract

Cutaneous Squamous Cell Carcinoma (cSCC) is the second most common type of non-melanoma skin cancer in white-skinned populations. cSCC is associated with sun exposure and aging, which is concomitant with an accumulation of senescent cells in the skin. The involvement of senescent cells in carcinogenesis has been highlighted in several cancer types and an interaction between cSCC cells and senescent cells is proposed, but still little explored. Tumor-associated effects are mostly attributed to the senescence-associated secretory phenotype (SASP). Here, we compared two in vitro models of senescence, namely replicative senescence and UVB-stress induced premature senescence (UVB-SIPS), in human dermal fibroblasts and screened for expression of SASP-related genes in our models. Next, the impact of senescent fibroblasts on three cSCC isogenic cell lines, representing different stages of keratinocyte malignant transformation, was studied. Only a limited impact on cSCC cell lines’ growth and migration has been detected with conditioned media collected from senescent fibroblasts and indirect co-cultures. We then investigated the opposite interaction and found that cSCC cell lines maintained in indirect co-cultures with fibroblasts induced and reinforced their senescence state as shown by an increased proportion of cells positive for the senescence-associated β-galactosidase activity and an increased expression of several SASP-related genes. Moreover, these effects were modulated according to the stage of tumorigenesis of the different cSCC cell lines used. Finally, cSCC cell lines-co-cultures are associated with NF-κB activation in HDFs. Understanding the interplay between tumor cells and their microenvironment may have important influences in cancer research and therapeutic strategies.

Original languageEnglish
Pages (from-to)113-126
Number of pages14
JournalInternational Journal of Biochemistry and Cell Biology
Volume98
DOIs
Publication statusPublished - 1 May 2018

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Fibroblasts
Squamous Cell Carcinoma
Carcinogenesis
Cells
Cell Line
Skin
Cell culture
Coculture Techniques
Cell Aging
Tumors
Phenotype
Genes
Galactosidases
Neoplasms
Epithelial Cells
Therapeutic Human Experimentation
Cellular Microenvironment
Conditioned Culture Medium
Sun
Skin Neoplasms

Keywords

  • Cutaneous squamous cell carcinoma
  • Senescence
  • Senescence-associated secretory phenotype, SASP
  • Skin
  • Stress-induced premature senescence, SIPS
  • UVB

Cite this

@article{5d5c58cf63984c518dd284d380f386cd,
title = "Unraveling the interplay between senescent dermal fibroblasts and cutaneous squamous cell carcinoma cell lines at different stages of tumorigenesis",
abstract = "Cutaneous Squamous Cell Carcinoma (cSCC) is the second most common type of non-melanoma skin cancer in white-skinned populations. cSCC is associated with sun exposure and aging, which is concomitant with an accumulation of senescent cells in the skin. The involvement of senescent cells in carcinogenesis has been highlighted in several cancer types and an interaction between cSCC cells and senescent cells is proposed, but still little explored. Tumor-associated effects are mostly attributed to the senescence-associated secretory phenotype (SASP). Here, we compared two in vitro models of senescence, namely replicative senescence and UVB-stress induced premature senescence (UVB-SIPS), in human dermal fibroblasts and screened for expression of SASP-related genes in our models. Next, the impact of senescent fibroblasts on three cSCC isogenic cell lines, representing different stages of keratinocyte malignant transformation, was studied. Only a limited impact on cSCC cell lines’ growth and migration has been detected with conditioned media collected from senescent fibroblasts and indirect co-cultures. We then investigated the opposite interaction and found that cSCC cell lines maintained in indirect co-cultures with fibroblasts induced and reinforced their senescence state as shown by an increased proportion of cells positive for the senescence-associated β-galactosidase activity and an increased expression of several SASP-related genes. Moreover, these effects were modulated according to the stage of tumorigenesis of the different cSCC cell lines used. Finally, cSCC cell lines-co-cultures are associated with NF-κB activation in HDFs. Understanding the interplay between tumor cells and their microenvironment may have important influences in cancer research and therapeutic strategies.",
keywords = "Cutaneous squamous cell carcinoma, Senescence, Senescence-associated secretory phenotype, SASP, Skin, Stress-induced premature senescence, SIPS, UVB",
author = "Marie Toutfaire and Elise Dumortier and Antoine Fattaccioli and {Van Steenbrugge}, Martine and Proby, {Charlotte M.} and Florence Debacq-Chainiaux",
year = "2018",
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language = "English",
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T1 - Unraveling the interplay between senescent dermal fibroblasts and cutaneous squamous cell carcinoma cell lines at different stages of tumorigenesis

AU - Toutfaire, Marie

AU - Dumortier, Elise

AU - Fattaccioli, Antoine

AU - Van Steenbrugge, Martine

AU - Proby, Charlotte M.

AU - Debacq-Chainiaux, Florence

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Cutaneous Squamous Cell Carcinoma (cSCC) is the second most common type of non-melanoma skin cancer in white-skinned populations. cSCC is associated with sun exposure and aging, which is concomitant with an accumulation of senescent cells in the skin. The involvement of senescent cells in carcinogenesis has been highlighted in several cancer types and an interaction between cSCC cells and senescent cells is proposed, but still little explored. Tumor-associated effects are mostly attributed to the senescence-associated secretory phenotype (SASP). Here, we compared two in vitro models of senescence, namely replicative senescence and UVB-stress induced premature senescence (UVB-SIPS), in human dermal fibroblasts and screened for expression of SASP-related genes in our models. Next, the impact of senescent fibroblasts on three cSCC isogenic cell lines, representing different stages of keratinocyte malignant transformation, was studied. Only a limited impact on cSCC cell lines’ growth and migration has been detected with conditioned media collected from senescent fibroblasts and indirect co-cultures. We then investigated the opposite interaction and found that cSCC cell lines maintained in indirect co-cultures with fibroblasts induced and reinforced their senescence state as shown by an increased proportion of cells positive for the senescence-associated β-galactosidase activity and an increased expression of several SASP-related genes. Moreover, these effects were modulated according to the stage of tumorigenesis of the different cSCC cell lines used. Finally, cSCC cell lines-co-cultures are associated with NF-κB activation in HDFs. Understanding the interplay between tumor cells and their microenvironment may have important influences in cancer research and therapeutic strategies.

AB - Cutaneous Squamous Cell Carcinoma (cSCC) is the second most common type of non-melanoma skin cancer in white-skinned populations. cSCC is associated with sun exposure and aging, which is concomitant with an accumulation of senescent cells in the skin. The involvement of senescent cells in carcinogenesis has been highlighted in several cancer types and an interaction between cSCC cells and senescent cells is proposed, but still little explored. Tumor-associated effects are mostly attributed to the senescence-associated secretory phenotype (SASP). Here, we compared two in vitro models of senescence, namely replicative senescence and UVB-stress induced premature senescence (UVB-SIPS), in human dermal fibroblasts and screened for expression of SASP-related genes in our models. Next, the impact of senescent fibroblasts on three cSCC isogenic cell lines, representing different stages of keratinocyte malignant transformation, was studied. Only a limited impact on cSCC cell lines’ growth and migration has been detected with conditioned media collected from senescent fibroblasts and indirect co-cultures. We then investigated the opposite interaction and found that cSCC cell lines maintained in indirect co-cultures with fibroblasts induced and reinforced their senescence state as shown by an increased proportion of cells positive for the senescence-associated β-galactosidase activity and an increased expression of several SASP-related genes. Moreover, these effects were modulated according to the stage of tumorigenesis of the different cSCC cell lines used. Finally, cSCC cell lines-co-cultures are associated with NF-κB activation in HDFs. Understanding the interplay between tumor cells and their microenvironment may have important influences in cancer research and therapeutic strategies.

KW - Cutaneous squamous cell carcinoma

KW - Senescence

KW - Senescence-associated secretory phenotype, SASP

KW - Skin

KW - Stress-induced premature senescence, SIPS

KW - UVB

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U2 - 10.1016/j.biocel.2018.03.005

DO - 10.1016/j.biocel.2018.03.005

M3 - Article

VL - 98

SP - 113

EP - 126

JO - The international journal of Biochemistry & Cell biology

JF - The international journal of Biochemistry & Cell biology

SN - 1357-2725

ER -