CANCER STEM CELLLas células madre del cáncer

Ramón Barceló

Hospital de Basurto

9 de junio de 2010

Stem cells, cancer, and cancer stem cells.Reya T, Morrison SJ, Clarke MF, Weissman IL.Nature. 2001 Nov 1;414(6859):105-11.

CSCs have recently been identified in several tumors, including cancers of the:

•Brain

•Breast

•Colon

•Ovary

•Pancreas

•Prostate

•Leukemia

Hidalgo M. N Engl J Med 2010;362:1605-1617

Jimeno A, et al. Mol Cancer Ther February 2009 8;310 A direct pancreatic cancer xenograft model as a platform for cancer stem cell therapeutic development

CD24

CD44

ALDH

Nestin

Hedgehog pathway

The Hedgehog Pathway and Pancreatic CancerManuel Hidalgo, and Anirban MaitraNEJM 2009 361:2094-2096

Distinct Populations of Cancer Stem Cells Determine Tumor Growth and Metastatic Activity in Human Pancreatic CancerHermann PC, Huber SL, Herrler T, et al. Cell Stem Cell 2007;1:313-323

These data demonstrate for the first time that in the utilized in vivo system a specific CD133+ CXCR4+ CSC subpopulation is the only population responsible for tumor metastasis.

CD26 is a110 kDa cell surface glycoprotein with intrinsic dipeptidyl peptidase IV(DPPIV) activity expressed on a variety of cell types including T lymphocyte, endothelial cells, and epithelial cells, and it is known to have multiple biological

functions

A Subpopulation of CD26+ Cancer Stem Cells with Metastatic Capacity in Human Colorectal Cancer. Pang R et al. Cell Stem Cell, Volume 6, Issue 6, 603-615, 4 June 2010

A. Behdad, S. BoseCedars-Sinai Medical Center, Los Angeles, CAJ Clin Oncol 28, 2010 (suppl; abstr e21108)

Expression of multiple cancer stem cell markers by triple-negative breast carcinomas.

Expression of multiple cancer stem cell markers is highly associated with triple negative breast carcinomas and in carcinomas expressing basal cytokeratins

Notch 1 and Notch 3 and prognosis of resected non-small cell lung cancerE. Cho, et alJ Clin Oncol 28, 2010 (suppl; abstr e21089)

The four mammalian Notch genes (Notch1-4) encode 300kDa single-pass transmembrane receptors.

Notch can variously serve as an oncogene or a tumor suppressor, a repressor or inducer of terminal differentiation, and perhaps a cancer stem cell factor in specific contexts.

Oncogenic Notch signaling is found in T-acute lymphoblastic leukemia/lymphoma (T-ALL), prostate, ovarian cancer, melanoma and breast cancer.

Notch 1 showed higher expression on squamous cell carcinoma. Neither Notch 1 nor 3 have correlated with RFS or OS, but patients with both expressions had the tendency of longer overall survival.

Prognostic value of hedgehog signaling in cervical carcinomaChaudary N, et al.J Clin Oncol 28, 2010 (suppl; abstr e15522)

Members of the Hh pathway are expressed in cervical cancer

There is limited correlation with tumor microenvironment

And no correlation with DFS

Ning Y et al.J Clin Oncol 28:7s, 2010 (suppl; abstr 4047)

Association of germline polymorphisms in genes involved in the CD44 pathway and clinical outcome in localized gastric adenocarcinoma (GA).

CD44 is a transmembrane glycoprotein serving as receptor of hyaluronan and osteopontin, is associated with adhesion and metastasis in gastrointestinal carcinomas and increased resistance for chemotherapy- or radiation-induced cell death.

This study identified germline variants within the CD44 gene as independent prognostic markers in localized GA.

Xu Y et al.J Clin Oncol 28:7s, 2010 (suppl; abstr 10568)

Relationship of expression level of CD133 with tumor angiogenesis and prognosis of hepatocellular carcinoma after liver transplantation

High expression level of CD133 is related to tumor angiogenesis and poor prognosis of HCC patients after liver transplantation

MUCHAS GRACIAS