[ RadSafe ] cancer is the result of defective tissue/immune control

[Rainer.Facius at dlr.de]

For those who always knew that (at least murine gastrointestinal) cancer is the result of defective tissue/immune control.

"The results support the concept that cancer, as an outcome, reflects the loss of the normal communication between the cellular constituents of a given organ8, and indicate that Smad4-deficient T cells ultimately send the wrong message to their stromal and epithelial neighbours."

http://www.nature.com/nature/journal/v441/n7096/full/nature04846.html 


Regards, Rainer

Dr. Rainer Facius
German Aerospace Center
Institute of Aerospace Medicine
Linder Hoehe
51147 Koeln
GERMANY
Voice: +49 2203 601 3147 or 3150
FAX:   +49 2203 61970

Nature 441, 1015-1019 (22 June 2006) | doi:10.1038/nature04846; Received 9 February 2006; Accepted 28 April 2006

Byung-Gyu Kim1, Cuiling Li2, Wenhui Qiao2, Mizuko Mamura1, Barbara Kasperczak3, Miriam Anver3, Lawrence Wolfraim1, Suntaek Hong1, Elizabeth Mushinski4, Michael Potter4, Seong-Jin Kim1, Xin-Yuan Fu5, Chuxia Deng2 and John J. Letterio1

Smad4 signalling in T cells is required for suppression of gastrointestinal cancer

Abstract

SMAD4 (MAD homologue 4 (Drosophila)), also known as DPC4 (deleted in pancreatic cancer), is a tumour suppressor gene that encodes a central mediator of transforming growth factor- signalling1, 2, 3, 4. Germline mutations in SMAD4 are found in over 50% of patients with familial juvenile polyposis, an autosomal dominant disorder characterized by predisposition to hamartomatous polyps and gastrointestinal cancer5, 6. Dense inflammatory cell infiltrates underlay grossly normal appearing, non-polypoid colonic and gastric mucosa of patients with familial juvenile polyposis7. This prominent stromal component suggests that loss of SMAD4-dependent signalling in cells within the epithelial microenvironment has an important role in the evolution of intestinal tumorigenesis in this syndrome. Here we show that selective loss of Smad4-dependent signalling in T cells leads to spontaneous epithelial cancers throughout the gastrointestinal tract in mice, whereas epithelial-specific deletion of the Smad4 gene does not. Tumours arising within the colon, rectum, duodenum, stomach and oral cavity are stroma-rich with dense plasma cell infiltrates. Smad4-/- T cells produce abundant TH2-type cytokines including interleukin (IL)-5, IL-6 and IL-13, known mediators of plasma cell and stromal expansion. The results support the concept that cancer, as an outcome, reflects the loss of the normal communication between the cellular constituents of a given organ8, and indicate that Smad4-deficient T cells ultimately send the wrong message to their stromal and epithelial neighbours.