Fibroblast-derived dermal matrix drives development of aggressive cutaneous squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa. / Ng, Yi-Zhen; Pourreyron, Celine; Salas-Alanis, Julio C.; Dayal, Jasbani H. S.; Cepeda-Valdes, Rodrigo; Yan, Wenfei; Wright, Sheila; Chen, Mei; Fine, Jo-David; Hogg, Fiona J.; McGrath, John A.; Murrell, Dedee F.; Leigh, Irene M.; Lane, E. Birgit; South, Andrew P.
In: Cancer Research, Vol. 72, No. 14, 2012, p. 3522-3534.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Fibroblast-derived dermal matrix drives development of aggressive cutaneous squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa
A1 - Ng,Yi-Zhen
A1 - Pourreyron,Celine
A1 - Salas-Alanis,Julio C.
A1 - Dayal,Jasbani H. S.
A1 - Cepeda-Valdes,Rodrigo
A1 - Yan,Wenfei
A1 - Wright,Sheila
A1 - Chen,Mei
A1 - Fine,Jo-David
A1 - Hogg,Fiona J.
A1 - McGrath,John A.
A1 - Murrell,Dedee F.
A1 - Leigh,Irene M.
A1 - Lane,E. Birgit
A1 - South,Andrew P.
AU - Ng,Yi-Zhen
AU - Pourreyron,Celine
AU - Salas-Alanis,Julio C.
AU - Dayal,Jasbani H. S.
AU - Cepeda-Valdes,Rodrigo
AU - Yan,Wenfei
AU - Wright,Sheila
AU - Chen,Mei
AU - Fine,Jo-David
AU - Hogg,Fiona J.
AU - McGrath,John A.
AU - Murrell,Dedee F.
AU - Leigh,Irene M.
AU - Lane,E. Birgit
AU - South,Andrew P.
PY - 2012
Y1 - 2012
N2 - Patients with the genetic skin blistering disease recessive dystrophic epidermolysis bullosa (RDEB) develop aggressive cutaneous squamous cell carcinoma (cSCC). Metastasis leading to mortality is greater in RDEB than in other patient groups with cSCC. Here we investigate the dermal component in RDEB using mRNA expression profiling to compare cultured fibroblasts isolated from individuals without cSCC and directly from tumor matrix in RDEB and non-RDEB samples. Although gene expression of RDEB normal skin fibroblasts resembled that of cancer-associated fibroblasts, RDEB cancer-associated fibroblasts exhibited a distinct and divergent gene expression profile, with a large proportion of the differentially expressed genes involved in matrix and cell adhesion. RDEB cancer-associated fibroblasts conferred increased adhesion and invasion to tumor and non-tumor keratinocytes. Reduction of COL7A1, the defective gene in RDEB, in normal dermal fibroblasts led to increased type XII collagen, thrombospondin-1, and Wnt-5A, while reexpression of wild type COL7A1 in RDEB fibroblasts decreased type XII collagen, thrombospondin-1, and Wnt-5A expression, reduced tumor cell invasion in organotypic culture, and restricted tumor growth in vivo. Overall, our findings show that matrix composition in patients with RDEB is a permissive environment for tumor development, and type VII collagen directly regulates the composition of matrix proteins secreted by dermal and cancer-associated fibroblasts. ©2012 AACR.
AB - Patients with the genetic skin blistering disease recessive dystrophic epidermolysis bullosa (RDEB) develop aggressive cutaneous squamous cell carcinoma (cSCC). Metastasis leading to mortality is greater in RDEB than in other patient groups with cSCC. Here we investigate the dermal component in RDEB using mRNA expression profiling to compare cultured fibroblasts isolated from individuals without cSCC and directly from tumor matrix in RDEB and non-RDEB samples. Although gene expression of RDEB normal skin fibroblasts resembled that of cancer-associated fibroblasts, RDEB cancer-associated fibroblasts exhibited a distinct and divergent gene expression profile, with a large proportion of the differentially expressed genes involved in matrix and cell adhesion. RDEB cancer-associated fibroblasts conferred increased adhesion and invasion to tumor and non-tumor keratinocytes. Reduction of COL7A1, the defective gene in RDEB, in normal dermal fibroblasts led to increased type XII collagen, thrombospondin-1, and Wnt-5A, while reexpression of wild type COL7A1 in RDEB fibroblasts decreased type XII collagen, thrombospondin-1, and Wnt-5A expression, reduced tumor cell invasion in organotypic culture, and restricted tumor growth in vivo. Overall, our findings show that matrix composition in patients with RDEB is a permissive environment for tumor development, and type VII collagen directly regulates the composition of matrix proteins secreted by dermal and cancer-associated fibroblasts. ©2012 AACR.
UR - http://www.scopus.com/inward/record.url?partnerID=yv4JPVwI&eid=2-s2.0-84863914039&md5=ba93f53453796143777e1ee26c9aa54d
U2 - 10.1158/0008-5472.CAN-11-2996
DO - 10.1158/0008-5472.CAN-11-2996
M1 - Article
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 14
VL - 72
SP - 3522
EP - 3534
ER -