The Pancreatic islets
The pancreas is both an exocrine and an endocrine gland. The exocrine functions are performed by acinar cells, which secrete digestive enzymes. The endocrine role is played by the pancreatic islets; group of cells comprising of alpha, beta, delta and PP cells that secretes insulin glucagon, somatostatin, and pancreatic polypeptide (PP) respectively.
Impaired pancreatic function is associated with severe pathologies ranging from chronic diabetes to cancer. Pancreatic adenocarcinoma in particular has poor prognosis and remains one of leading causes of cancer related deaths worldwide. Surgery remains the only treatment option, albeit with little success as most of the cancers are diagnosed at a late metastatic stage making surgery a bandage at best (Ryan et al, 2014). Thus it is of importance to develop adequate pre-clinical models to investigate the response to possible chemotherapeutic measures and personalized therapies. In this regard modern 2D and 3D cell cultures are particularly useful in establishing a reliable and reproducible system for pancreatic cancer studies (Ehlen et al, 2020).
The use of 3D cell culture models of adenocarcinoma
Recent advances in 3D cell culture systems of cancer cells (spheroids and organoids) completely replicate the in-vivo state of cancer cells with regards to cell-cell interactions, and mimic the microenvironment present within the cancer tissues (Ware et al, 2016). This feature is essential for drug response assays as environmental cues affect the behavior and function of cells, and subsequently affect the cellular response to therapeutic drugs. 3D cell culture models also offer in depth information on concentration gradients of signaling molecules and therapeutic agents, as well as reliable detail on structure of the extracellular matrix surrounding the cancer cells (Mellor et al 2005, Kunz-Schughart et al, 2004, Hicks et al, 2003).
Spheroids : a rapid, reliable and reproducible system
Spheroids are the popular 3D cell culture system used in cancer research. These self-assembled aggregates can be cultured using 96-well hanging drop plates, with cell repellent surface or ultra low attachment clear bottom 96 well plates. Compared to organoids, spheroids are relatively easy to maintain, is highly reproducible, making it a cost effective method for drug testing. Human pancreatic cell lines such as Panc-1 (human pancreatic cell line), Capan-1 (human pancreatic adenocarcinoma cells), MIA PaCa-2 (Human pancreatic cell line) can be successfully cultured as spheroids that are uniform, easy to handle, and highly reproducible (Ware et al, 2016). Other cell lines that can be used in spheroid cultures also include DAN-G (Human pancreas carcinoma cells), Panc-89 and FAMPAC (Human pancreatic adenocarcinoma cell line) (Ware et al, 2016).
References
1. https://opentextbc.ca/anatomyandphysiologyopenstax/chapter/the-endocrine-pancreas/
2. Ehlen, L., Arndt, J., Treue, D. et al. Novel methods for in vitro modeling of pancreatic cancer reveal important aspects for successful primary cell culture. BMC Cancer 20, 417 (2020). https://doi.org/10.1186/s12885-020-06929-8
3. Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N Engl J Med. 2014;371(11):1039–49.
4. Ware MJ, Colbert K, Keshishian V, et al. Generation of Homogenous Three-Dimensional Pancreatic Cancer Cell Spheroids Using an Improved Hanging Drop Technique. Tissue Eng Part C Methods. 2016;22(4):312-321. doi:10.1089/ten.TEC.2015.0280
5. Mellor H.R., Ferguson D.J., and Callaghan R. A model of quiescent tumour microregions for evaluating multicellular resistance to chemotherapeutic drugs. Br J Cancer 93, 302, 2005
6. Kunz-Schughart L.A., Freyer J.P., Hofstaedter F., and Ebner R. The use of 3-D cultures for high-throughput screening: the multicellular spheroid model. J Biomol Screen 9, 273, 2004
7. Ware MJ, Keshishian V, Law JJ, et al. Generation of an in vitro 3D PDAC stroma rich spheroid model. Biomaterials. 2016;108:129-142. doi:10.1016/j.biomaterials.2016.08.041
8. Yeon S-E, No DY, Lee S-H, Nam SW, Oh I-H, Lee J, et al. (2013) Application of Concave Microwells to Pancreatic Tumor Spheroids Enabling Anticancer Drug Evaluation in a Clinically Relevant Drug Resistance Model. PLoS ONE 8(9): e73345. https://doi.org/10.1371/journal.pone.0073345
