Title: Basement membrane and its role in tumor invasion and metastasis (500 words) 1.

Describe the structure and composition of the basement membrane (180 words) 2. Briefly describe the function of the basement membrane (70 words) 3. Discuss the role of the basement membrane in tumor invasion (180 words) words)

4. Briefly describe the role of proteases in the local degradation of the basement membrane (70

The basement membrane is a sheet-like arrangement of extracellular proteins acting as an interface between parenchymal cells and their support tissues. It is associated with epithelial and muscles cells, as well as the central nervous system. It is made up of three layers lamina lucida, which lines lamina fibroreticularis, which merges with the underlying supporting tissue.

the basal cell membrane of parenchymal tissue; the intermediate layer, lamina densa; and the

The main constituents of the basement membrane are heparan sulphate, collagen type IV,

fibronectin, laminin and entactin. Both lamina lucida and lamina densa are made of a mesh of type proteoglycan heparan sulphate, as well as to laminin receptors in parenchymal basal plasma

IV collagen. Laminin then binds this mesh to other basement membrane constituents, such as the membranes. The binding of laminin to type IV collagen is mediated by entactin. Lamina fibroreticularis represents a condensation of the underlying supporting tissue and is constituted mainly of type III collagen, which is bound to integrins in parenchymal basal plasma membrane via fibronectin. All three layers are anchored together by type VII collagen fibrils.

The basement membrane has five functions. First and foremost, it serves as an intermediary structural attachment between epithelial cells and adjacent connective tissue. Second, it helps with compartmentalization by separating epithelia, nerve and muscle tissues from connective tissue. spaces and ionic charges. Fourth, it aids in epithelial polarity induction by influencing the structure of basal membrane surfaces. Last but not least, it acts as a scaffold during tissue regeneration, helping the regenerated tissue to retain original tissue architecture.

Third, it regulates substance exchange between epithelial and connective tissues, through integral

A tumor is said to be benign when it remains localized, restricted from spreading by the basement membrane. Benign tumors can be surgically removed, and the patient usually survives. However, when the lesion invades and destroys the basement membrane, it is classified as malignant. The cancerous primary tumor can then metastasize to other tissues and cause death.

The metastatic cascade begins when cells detach from the primary tumor and breach the basement membrane. They then traverse the extracellular matrix, gain access to circulation by penetrating the vascular basement membrane, and extravasate at a distant site, forming a metastatic tumor.

As mentioned earlier, since the basement membrane acts as a physical barrier between epithelia and stroma, malignant tumors will have to break it down to proliferate beyond the primary lesion site. Both the epithelial and vascular basement membranes are degraded by proteases, secreted either by

Title: Basement membrane and its role in tumor invasion and metastasis (500 words) 1. Describe the structure and composition of the basement membrane (180 words) 2. Briefly describe the function of the basement membrane (70 words) 3. Discuss the role of the basement membrane in tumor invasion (180 words) words)

4. Briefly describe the role of proteases in the local degradation of the basement membrane (70

tumor cells themselves, or through their inducing of stromal cells. An example would be the matrix growth factors sequestered in the extracellular matrix. These growth factors then promote

metalloproteinases, which remodel insoluble components of the basement membrane, and release chemotaxis and angiogenesis, further aiding cancer metastasis. It has also been observed that the the exact mechanism has yet to be fully elucidated.

basement membrane aids in micrometastasis through promotion of tumor cell dormancy, though

Pelengaris S (ed.), Khan M (ed.). The Molecular Biology of Cancer. Cornwall: Blackwell Publishing Ltd; 2006 Junqueira LC, Carneiro J. Basic Histology: text & atlas. 11th edition. USA: The McGraw-Hill Companies, Inc.; 2005 Pogny G, Timr F, Olh J, Harisi R, Polony G, Paku S, Bocsi J, Jeney A, Laurie GW. Role of the Basement Membrane in Tumor Cell Dormancy and Cytotoxic Resistance. Oncology [Online] 2001;60(3):274-281. Available from 2013]

http://people.virginia.edu/~gwl6s/home.html/pdfs/Pogany.et.al.Oncol.01.pdf [Accessed 17 May Kumar V, Abbas AK, Fausto N, Aster JC. Robbins and Cotran Pathologic Basis of Disease. 8th edition. Philadelphia: Elsevier Inc; 2010 Young B, Lowe JS, Stevens A, Heath JW. Wheater's Functional Histology: A Text and Colour Atlas. 5th edition. Philadelphia: Elsevier Inc; 2006