PRL-3 overexpression in epithelial cells is induced by surrounding stromal fibroblasts.
We isolate and culture carcinoma-associated fibroblasts (CAFs) from primary tumour (CAFpt), CAFs from corresponding synchronous liver metastasis (CAFlm) as well as normal colonic fibroblasts (NCF) from the same patient. From these cultures, conditioned media (CM) was obtained. Culture of a wide panel of colorectal and pancreatic cell lines in CM from CAFlm resulted in overexpression of mRNA PRL-3 and higher overexpression in CAFs than in non-activated fibroblasts. Moreover PRL-3 mRNA expression correlates with expression of alpha-SMA and deposition of collagen fibrils in the stroma. We demonstrate that products secreted by CAFs trigger PRL-3 overexpression in cancer cells. Identification of these factors may contribute to new stroma-targeted therapies for desmoplastic tumours.
Molleví
David G
DG
Translational Research Laboratory, Institut Català d'Oncologia, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), 08907 L'Hospitalet de Llobregat, Barcelona, Spain. dgmollevi@iconcologia.net
Aytes
Alvaro
A
Berdiel
Mireia
M
Padullés
Laura
L
Martínez-Iniesta
Maria
M
Sanjuan
Xavier
X
Salazar
Ramon
R
Villanueva
Alberto
A
D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D017077:Culture Media, Conditioned; D004847:Epithelial Cells / Q000201:enzymology; D005347:Fibroblasts / Q000201:enzymology*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000235:genetics; D017154:Stromal Cells / Q000201:enzymology
D017077:Culture Media, Conditioned; D009363:Neoplasm Proteins; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases