Publication Date

8-2024

Advisor(s) - Committee Chair

Ajay Srivastava, Moon-Soo Kim, Joseph Marquardt

Degree Program

Department of Biology

Degree Type

Master of Science

Abstract

Cysteine cathepsins, particularly cathepsins L and B, play crucial roles in cancer cell migration and metastasis by promoting extracellular matrix degradation, and activating signaling pathways that enhance tumor cell growth and inflammation. In this study, we investigate the role of cathepsin L in tumor metastasis, specifically CP1 in Drosophila melanogaster, as an ortholog to human cathepsin L. Previous research has shown that CP1 is involved in tissue development and invasive behavior during Drosophila Air Sac Primordium development. Leveraging the genetic similarities between Drosophila and humans, the fruit fly serves as a model organism to study tumor metastasis.

Using techniques like the MARCM (Mosaic Analysis with a Repressible Cell Marker) system, GAL4/UAS system, and RNA interference (RNAi), we induced tumor growth and assayed for CP1 expression levels to further analyze its role in tumor growth, and invasion. Its potential for activation of matrix metalloproteinase 1 (DmMmp1), a crucial enzyme in tumor metastasis was also studied. Immunohistochemistry and Western blot analysis were employed to assess CP1 expression in benign and metastatic tumors.

Our results demonstrate dynamic changes in CP1 expression levels during tumor progression, with higher expression observed in metastatic tumors compared to benign tumors. Additionally, our preliminary study indicates that CP1 overexpression leads to a modest increase in cleaved MMP levels, suggesting that CP1 might play a role in this increase. Overall, our study attempts to clarify the role of CP1 in tumor metastasis and activation of matrix metalloproteinase 1.

Disciplines

Biology | Cell and Developmental Biology | Genetics and Genomics | Life Sciences

Available for download on Friday, July 23, 2027

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