A 68-year-old man comes to the office due to an enlarging mole on his right forearm. The patient is a retired farmer and received a significant amount of sun exposure over the course of his life. On examination, he has a black-brown macular lesion on the dorsum of his right forearm measuring approximately 1 cm in diameter with an irregular border. Excisional biopsy is performed and histopathology reveals malignant melanoma. Immunohistochemical analysis indicates that the malignant cells have decreased integrin expression. These cells are most likely to exhibit poor adhesion to which of the following components of the extracellular matrix?

Question

A 68-year-old man comes to the office due to an enlarging mole on his right forearm.  The patient is a retired farmer and received a significant amount of sun exposure over the course of his life.  On examination, he has a black-brown macular lesion on the dorsum of his right forearm measuring approximately 1 cm in diameter with an irregular border.  Excisional biopsy is performed and histopathology reveals malignant melanoma.  Immunohistochemical analysis indicates that the malignant cells have decreased integrin expression.  These cells are most likely to exhibit poor adhesion to which of the following components of the extracellular matrix?

Quizplus · Accepted Answer

11ec160b_3696_3e70_9249_af859b9f5df2_MD0001_00 Cellular adhesion is the means by which one cell binds to another cell, surface, or matrix. The integrins are a family of transmembrane protein receptors that interact with the extracellular matrix by binding to specific proteins, including collagen, fibronectin, and laminin. Other adhesion molecule classes include the cadherins, selectins, and Ig superfamily members. Fibronectins are large glycoproteins produced by fibroblasts and some epithelial cells. Fibronectin binds to integrins, matrix collagen, and glycosaminoglycans, serving as a mediator of cell adhesion and migration. Differential expression of integrin subtypes affects adhesion properties of individual cells, and correlates with malignant behavior in a number of tumors, including melanoma. (Choices A and E) The intracellular domains of the integrins interact with a number of structural proteins, including microfilaments (actin) within the cytoplasm and intermediate filaments (keratin). However, the extracellular domains do not interact with these structures. (Choices C and D) Hyaluronic acid is a glycosaminoglycan that contributes to water retention in the extracellular matrix, and determines the stiffness of the matrix. Keratan sulfate is a glycosaminoglycan in the extracellular matrix that may play a role in maintaining type I collagen fibril organization in a number of tissues (eg, cornea). However, neither of these is a ligand for integrins. Educational objective: Adhesion of cells to the extracellular matrix involves integrin-mediated binding to fibronectin, collagen, and laminin. Differential expression of integrin subtypes affects adhesion properties of individual cells, and has been found to correlate with malignant behavior in a number of tumors. __________ References: Integrins: versatile receptors controlling melanocyte adhesion, migration, and proliferation. (http://www.ncbi.nlm.nih.gov/pubmed/21087420)

A 68-Year-Old Man Comes to the Office Due to an Enlarging