Abstract

Prostate cancer (PC) is one of the most common male cancers in United States. PC lethality is due to metastatic growth, when cancer cells move from the primary tumor site to a secondary site. A key step is the acquisition of motility. Connexins (Cx) play a major role in cell-cell communication and contribute to motility. Cx43 is up-regulated in cultured PC3 metastatic prostate cancer cells. To understand the role of Cx43 in migration we asked whether silencing Connexin 43 would decrease PC3 cell migration. Using cells in which short interfering RNA (si-RNA) silenced Cx43 mRNA, we showed that silencing Cx43 decreased motility of si-Cx43 PC3 cells in Boyden chamber assays. To confirm these results in another biological system, we performed cellular wound healing assays. Silencing Cx43 decreased motility of PC3 cells reducing movement to wounded area, leaving more area open in the Cx43 inhibited cell lines. These results supported those of our Boyden assays showing that loss of Cx43 decreases the migration ability of PC3. Next we asked whether overexpression of Cx43 in LNCaP cells, non-migratory prostate cancer cells that lack Cx43 expression, would increase their motility. Currently we are working to engineer Cx43 expression in a modified LNCaP cell line. A comparison of cell lines engineered to overexpress or to silence Cx43 will confirm the importance of Cx43 in the motility of prostate cancer cells in vitro. Cx43 relevance will later be tested in vivo and could lead to new targeting strategies for men suffering from metastatic prostate cancer.

Modified Abstract

Prostate cancer (PC) is one of the most common male cancers in the United States. PC lethality is due to its ability to metastasize, which is where the cancer cells move from the primary tumor site to a secondary site. We looked at a protein called Connexin 43 (Cx43) which is known to be produced at a higher rate in some prostate cancer cells. Our experiment involved first silencing the production of Cx43 in metastasizing prostate cancer cells then measuring whether the cells ability to migrate was affected. We found that inhibiting Cx43 production did reduce migration. The next step is measuring whether increasing Cx43 in non-migratory cells increases their motility. We hope that this will lead to new targeting strategies for PC treatment.

Research Category

Biology/Ecology

Primary Author's Major

Biology

Mentor #1 Information

Dr Gail Fraizer

Presentation Format

Poster

Start Date

March 2017

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Research Area

Male Urogenital Diseases | Oncology

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Mar 21st, 1:00 PM

Does Cx43 Modulate the Motility of Prostate Cancer Cells

Prostate cancer (PC) is one of the most common male cancers in United States. PC lethality is due to metastatic growth, when cancer cells move from the primary tumor site to a secondary site. A key step is the acquisition of motility. Connexins (Cx) play a major role in cell-cell communication and contribute to motility. Cx43 is up-regulated in cultured PC3 metastatic prostate cancer cells. To understand the role of Cx43 in migration we asked whether silencing Connexin 43 would decrease PC3 cell migration. Using cells in which short interfering RNA (si-RNA) silenced Cx43 mRNA, we showed that silencing Cx43 decreased motility of si-Cx43 PC3 cells in Boyden chamber assays. To confirm these results in another biological system, we performed cellular wound healing assays. Silencing Cx43 decreased motility of PC3 cells reducing movement to wounded area, leaving more area open in the Cx43 inhibited cell lines. These results supported those of our Boyden assays showing that loss of Cx43 decreases the migration ability of PC3. Next we asked whether overexpression of Cx43 in LNCaP cells, non-migratory prostate cancer cells that lack Cx43 expression, would increase their motility. Currently we are working to engineer Cx43 expression in a modified LNCaP cell line. A comparison of cell lines engineered to overexpress or to silence Cx43 will confirm the importance of Cx43 in the motility of prostate cancer cells in vitro. Cx43 relevance will later be tested in vivo and could lead to new targeting strategies for men suffering from metastatic prostate cancer.