Notch Signaling in Melanoma-Modulated Osteoclastogenesis
Faculty Mentor
Jason Ashley
Presentation Type
Poster
Start Date
5-8-2024 11:15 AM
End Date
5-8-2024 1:00 PM
Location
PUB NCR
Primary Discipline of Presentation
Biology
Abstract
Melanoma, a cancer originating from mutated melanocyte (pigment-producing) cells, is primarily present in the skin but may spread to other organs. If the melanoma tumor becomes malignant, it can invade other organs via the cardiovascular and lymphatic systems. Metastatic melanoma in the bone is capable of inducing osteoclastogenesis, leading to an increase in lacunar bone resorption. Associated symptoms include bone pain, pathological fractures, hypercalcemia, and neurological symptoms due to spinal cord and nerve compression. The Notch signaling pathway is a cell-contact-dependent pathway that regulates cell proliferation, cell fate, differentiation, and apoptosis in all multicellular animals. Based on prior evidence of Notch signaling’s essential nature to osteoclast differentiation, we hypothesize that Notch signaling is utilized in the communication between metastatic melanoma cells and osteoclasts. In this study, we plan to explore the change in differentiation rates of osteoclasts from bone marrow macrophages in the presence of A375 melanoma cells with typical and altered Notch signaling capacities. Modified A375 cells will express one of two Notch pathway inhibitory proteins, dominant negative Mastermind-like or dominant negative Mindbomb-1, or enhanced green fluorescent protein as a control. After this initial stage, we will measure melanoma cell proliferation and viability and the resultant osteoclastogenesis when co-cultured with osteoclast precursors. Alterations in the behavior of A375 cells or their ability to influence osteoclast differentiation will be evidence of a role for Notch signaling. Completion of this work will provide a strong foundation for future research based on this specific interaction between the two cell populations.
Recommended Citation
Kaddoura, Mohammad and Patterson, Mamiko, "Notch Signaling in Melanoma-Modulated Osteoclastogenesis" (2024). 2024 Symposium. 24.
https://dc.ewu.edu/srcw_2024/ps_2024/p2_2024/24
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Notch Signaling in Melanoma-Modulated Osteoclastogenesis
PUB NCR
Melanoma, a cancer originating from mutated melanocyte (pigment-producing) cells, is primarily present in the skin but may spread to other organs. If the melanoma tumor becomes malignant, it can invade other organs via the cardiovascular and lymphatic systems. Metastatic melanoma in the bone is capable of inducing osteoclastogenesis, leading to an increase in lacunar bone resorption. Associated symptoms include bone pain, pathological fractures, hypercalcemia, and neurological symptoms due to spinal cord and nerve compression. The Notch signaling pathway is a cell-contact-dependent pathway that regulates cell proliferation, cell fate, differentiation, and apoptosis in all multicellular animals. Based on prior evidence of Notch signaling’s essential nature to osteoclast differentiation, we hypothesize that Notch signaling is utilized in the communication between metastatic melanoma cells and osteoclasts. In this study, we plan to explore the change in differentiation rates of osteoclasts from bone marrow macrophages in the presence of A375 melanoma cells with typical and altered Notch signaling capacities. Modified A375 cells will express one of two Notch pathway inhibitory proteins, dominant negative Mastermind-like or dominant negative Mindbomb-1, or enhanced green fluorescent protein as a control. After this initial stage, we will measure melanoma cell proliferation and viability and the resultant osteoclastogenesis when co-cultured with osteoclast precursors. Alterations in the behavior of A375 cells or their ability to influence osteoclast differentiation will be evidence of a role for Notch signaling. Completion of this work will provide a strong foundation for future research based on this specific interaction between the two cell populations.
