Breaking the Rules: Increased Invasive Agression in Chemo-Resistant Lymphoma
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Diffuse Large B Cell Lymphoma (DLBCL) is a common form of cancer, accounting for 30% of all lymphoma diagnoses. Patient survival rates of DLBCL are roughly 30-40% with the standard chemotherapeutic cocktail consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP therapy). Approximately 50% of patients develop chemoresistance to CHOP therapy and succumb to metastasis of vital organs. To penetrate tissues and organs, lymphoma cells must invade the extracellular matrix surrounding blood vessels. We investigated the ability of CHOP-resistant lymphoma to invade three-dimensional collagen matrices mimicking the extracellular matrix. We evaluated the potential for cellular dyes to quantify invasion responses and developed a protocol for automated fluorescent quantification of invasion responses. Further, because the cytoskeleton is critical for cell locomotion and morphology, we investigated the role of key cytoskeletal proteins vimentin, actin, and tubulin in lymphoma invasion. Our data indicate that microtubule stabilization, but not depolymerization, inhibits CHOP-resistant lymphoma invasion. Additionally, depolymerization of actin and vimentin completely blocked invasion responses. Altogether, this work develops a quantifiable model to study lymphoma invasion, mimic metastasis, understand cytoskeletal function, and gain further insight into molecular signals required for cellular invasion in three-dimensional matrices.
Cherry, Evan M (2010). Breaking the Rules: Increased Invasive Agression in Chemo-Resistant Lymphoma. Honors and Undergraduate Research. Available electronically from