Investigation of Conditioned Media-Mediated Communication between Pancreatic Cancer Cells and Neurons

Yıl 2025, Cilt: 8 Sayı: 1, 15 - 22, 28.02.2025

Didem Karakaş

https://doi.org/10.53446/actamednicomedia.1530253

Öz

Objective: Pancreatic cancer (PCa) is one of the deadliest cancers, characterized by prominent pathological changes in nerves. PCa cells invade nerves, termed neural invasion, driven by bidirectional interactions between cancer cells and nerves, leading to severe pain and shorter patient survival. However, the understanding of this communication remains limited, particularly in cell culture experiments. Therefore, we investigated the effect of soluble factors derived from neurons and PCa cells on behaviors of each cell type.

Material and Methods: SH-SY5Y cells were differentiated into neurons, and the differentiation efficacy was confirmed by immunofluorescence staining and Western blot. PANC-1 and BxPC-3 PCa cells were exposed to conditioned media (CM) from neurons, and changes in migration and invasion were evaluated by wound healing and transwell invasion assay, respectively. Similarly, neurons were treated with CM derived from PANC-1 or BxPC-3 cells, and changes in migration and neuronal markers were assessed.

Results: Neuron-derived CM showed no significant impact on PCa cell migration and invasion. Similarly, exposure of neurons from PCa cells did not significantly migration of them, but slightly increased neurite formation.

Conclusion: This study provided preliminary information on the possible effect of CM on the interaction between PCa cells and neurons. However, the absence of other cell types in the TME (such as fibroblasts and Schwann cells) in the study design might be a reason for not obtaining the expected changes. Therefore, different culture models and further research are needed to investigate the role of cells and factors that may potentially contribute to cancer-neuron interaction.

Anahtar Kelimeler

pancreatic cancer, neurons, conditoned media, cell migration, invasion

Pankreas Kanseri Hücreleri ve Nöronlar Arasında Koşullu Besiyeri Aracılı Etkileşimin Araştırılması

Öz

Amaç: Pankreas kanseri (PKa), sinirlerde belirgin patolojik değişikliklerle karakterize, en ölümcül kanserlerden biridir. Kanser hücreleri ve sinirler arasındaki çift yönlü etkileşimler sonucu PKa hücrelerinin sinirleri istila ettiği bilinmektedir. Nöral invazyon olarak adlandırılan bu durum, hastalarda şiddetli ağrı ve kısa sağkalım süreleriyle ilişkilidir. Sinirler ve kanser hücreleri arasındaki ilişkinin anlaşılmasına yönelik bazı çalışmalar bulunmakla birlikte, özellikle bu kapsamdaki hücre kültürü çalışmaları oldukça sınırlıdır. Bu nedenle, bu çalışmada, nöronlardan ve PKa hücrelerinden salınan faktörlerin her bir hücre tipinin davranışları üzerindeki etkisini araştırılmıştır.

Yöntem: SH-SY5Y hücreleri nöronlara farklılaştırıldı ve farklılaşma etkinliği immünofloresan boyama ve Western blot ile doğrulandı. PANC-1 ve BxPC-3 kanser hücreleri nöronlardan elde edilen koşullu besiyerine (CM) maruz bırakıldıktan sonra migrasyon ve invazyon yeteneklerindeki değişiklikler sırasıyla yara iyileşmesi ve matrijel invazyon deneyi ile değerlendirildi. Benzer şekilde, nöronlar PANC-1 veya BxPC-3 hücrelerinden elde edilen besiyerine maruz bırakıldı ve nöronların migrasyon ve nöronal belirteçlerdeki değişiklikler değerlendirildi.

Bulgular: Nöronlardan toplanan besiyerinin, PKa hücrelerinin migrasyon ve invazyonu üzerinde anlamlı bir etki göstermediği görüldü. Benzer şekilde, PKa hücrelerine ait besiyerinin nöronlara uygulanmasının, nöronların migrasyonunu anlamlı şekilde etkilemediği, ancak nörit oluşumunu arttırdığı bulundu.

Sonuç: Bu çalışma, PKa hücreleri ve nöronlar arasındaki karşılıklı etkileşimde koşullu besiyerinin olası etkisine dair öncül bilgi üretilmesine olanak sağlamıştır. Ancak, tümör mikroçevresindeki diğer hücre türlerinin (fibroblastlar ve Schwann hücreleri gibi) çalışma tasarımında yer almamasının beklenen değişikliklerin elde edilememesinde bir neden olabileceği düşünülmüştür. Bu nedenle, kanser-nöron etkileşimine potansiyel olarak katkı sağlayabilecek hücrelerin ve faktörlerin detaylı olarak incelenebilmesi için farklı kültür modellerine ve daha fazla araştırmaya ihtiyaç bulunmaktadır.

Anahtar Kelimeler

pankreas kanseri, nöron, koşullu besiyeri, hücre migrasyonu, invazyon

Kaynakça

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