| dc.description.abstract | 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. | en |
