The Role of Podoplanin in Tumor Progression and Metastasis
Thursday, November 27th, 2008.
Anticancer Research. 2008 Sep-Oct;28(5B):2997-3006. [Link]
Raica M, Cimpean AM, Ribatti D.
Department of Histology and Cytology, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania.
Abstract
In the last decade, much data has been generated concerning the molecular mechanisms of lymphangiogenesis and its significance in pathological conditions. This was mainly due to the discovery of lymphatic endothelial cell (LEC)-specific markers, such as vascular endothelial growth factor receptor-3 (VEGFR-3), LYVE-1, Prox-1 and podoplanin. Podoplanin, originally detected on the surface of podocytes, belongs to the family of type-1 transmembrane sialomucin-like glycoproteins. Although specific for lymphatic vascular (LV) endothelium, podoplanin is expressed in a wide variety of normal and tumor cells. The expression of podoplanin is induced by the homeobox gene Prox-1 and a specific endogenous receptor was identified on platelets. Immunohistochemical detection of podoplanin/D2-40 in LECs was used in many studies to evaluate the LV microvascular density (LVMD) in peritumoral and tumoral areas, and to correlate LVMD with lymph node status and prognosis. Podoplanin significantly increases the detection of lymphovascular invasion in different types of malignant tumors. Podoplanin expression was found in tumor cells of various types of cancer, such as vascular tumors, malignant mesothelioma, tumors of the central nervous system (CNS), germ cell tumors and squamous cell carcinomas. This expression in tumor cells is useful for pathological diagnosis and podoplanin seems to be expressed by aggressive tumors, with higher invasive and metastatic potential. Based on these data, podoplanin might be considered as an attractive therapeutic target for both LVs and tumor cells. Further studies are necessary to investigate differences in the expression of podoplanin in normal and tumor-associated lymphatics, and between the expression of podoplanin in normal non-LECs and tumor cells.
Keywords: Lymphatic vessels, metastasis, podoplanin, tumor growth
Glossary
- prognosis
- (prog-no-sis) a prediction of the course of disease; the outlook for the cure of the patient. For example, women with breast cancer that was detected early and who received prompt treatment have a good prognosis.
- metastasis
- (meh-tas-teh-sis) the spread of cancer cells to distant areas of the body by way of the lymph system or bloodstream.
- lymph
- (limf) clear fluid that flows through the lymphatic vessels and contains cells known as lymphocytes. These cells are important in fighting infections and may also have a role in fighting cancer.
- gene
- a segment of DNA that contains information on hereditary characteristics such as hair color, eye color, and height, as well as susceptibility to certain diseases. Women who have BRCA1 or BRCA2 gene mutations (defects) have an inherited tendency to develop breast cancer.
- diagnosis
- identifying a disease by its signs or symptoms, and by using imaging procedures and laboratory findings. The earlier a diagnosis of cancer is made, the better the chance for long-term survival.
- detection
- finding disease. Early detection means that the disease is found at an early stage, before it has grown large or spread to other sites. Note many forms of cancer can reach an advanced stage without causing symptoms. Mammography can help to find breast cancer early, and the PSA blood test is useful in finding prostate cancer.
- cytology
- (cy-tahl-uh-gee) the branch of science that deals with the structure and function of cells.
- cell
- the basic unit of which all living things are made. Cells replace themselves by splitting and forming new cells (mitosis). The processes that control the formation of new cells and the death of old cells are disrupted in cancer.
- cancer
- malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.
- tumor
- an abnormal lump or mass of tissue. Tumors can be benign (not cancerous) or malignant (cancerous).
- mesothelioma
- a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.
