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Decreased laminin adhesion and local extension
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Decreased laminin adhesion and spread via blood
Decreased laminin adhesion and spread via lymphatics
Increased laminin adhesion and spread via blood
Increased laminin adhesion and spread via lymphatics
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This patient who presents with new-onset bone pain, weight loss, and fatigue in the setting of prior renal cell carcinoma most likely has developed metastatic cancer. Renal cell carcinoma metastasizes after decreasing laminin adhesion followed by hematogenous spread to lymph nodes, lungs, and bones. Metastasis refers to the spread of a neoplasm to tissues that are distant from its site of origin. The requirements that must be met for a neoplasm to have metastatic potential include decreased adhesion to cytoskeletal elements such as the basement membrane, proximity to a blood vessel or lymphatic passage, and the ability to survive in the distant tissue. Neoplasms may spread either hematogenously or via lymphatics, with sarcomas most commonly spreading via blood and carcinomas most commonly spreading via lymphatics. The most notable exceptions to this general rule are renal cell carcinoma, follicular carcinoma of the thyroid, and hepatocellular carcinoma, as all of these carcinomas prefer hematogenous spread. Bagatur et al. show how tissue transglutaminase expression is required for metastasis of renal cell carcinomas. They find that this protein is critical in changing the adhesion of cells via fibronectin, collagen, and laminin. Incorrect Answers: Answer 1: Decreased laminin adhesion and local extension is incorrect because the bone pain is likely due to distant bony metastasis rather than local tumor spread. Answer 3: Decreased laminin adhesion and spread via lymphatics is incorrect because, unlike most carcinomas, renal cell carcinoma spreads via blood rather than lymphatics. Answer 4: Increased laminin adhesion and spread via blood is incorrect because increased adhesion to the basement membrane would anchor cells to the original site rather than allowing them to detach and spread hematogenously. Answer 5: Increased laminin adhesion and spread via lymphatics is incorrect because increased adhesion to the basement membrane would anchor cells to the original site rather than allowing them to detach and spread. In addition, unlike most carcinomas, renal cell carcinoma spreads via blood rather than lymphatics. Bullet Summary: Metastatic transformation of malignancies can be due to impaired adhesion to fibronectin, collagen, and laminin.
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