Title

Establishment of a Murine Pro-acinar Cell Line to Characterize Roles for FGF2 and α3β1 Integrins in Regulating Pro-acinar Characteristics

Document Type

Article

Publication Date

7-29-2019

DOI

10.1038/s41598-019-47387-y

Abstract

Radiation therapy for head and neck cancers results in permanent damage to the saliva producing acinar compartment of the salivary gland. To date, a pure pro-acinar cell line to study underlying mechanisms of acinar cell diferentiation in culture has not been described. Here, we report the establishment of a pro-acinar (mSG-PAC1) and ductal (mSG-DUC1) cell line, from the murine submandibular salivary gland (SMG), which recapitulate developmental milestones in diferentiation. mSG-DUC1 cells express the ductal markers, keratin-7 and keratin-19, and form lumenized spheroids. mSG-PAC1 cells express the pro-acinar markers SOX10 and aquaporin-5. Using the mSG-PAC1 cell line, we demonstrate that FGF2 regulates specifc steps during acinar cell maturation. FGF2 up-regulates aquaporin-5 and the expression of the α3 and α6 subunits of the α3β1 and α6β1 integrins that are known to promote SMG morphogenesis and diferentiation. mSG-DUC1 and mSG-PAC1 cells were derived from genetically modifed mice, homozygous for foxed alleles of the integrin α3 subunit. Similar to SMGs from α3-null mice, deletion of α3 alleles in mSG-PAC1 cells results in the up-regulation of E-cadherin and the downregulation of CDC42. Our data indicate that mSG-DUC1 and mSG-PAC1 cells will serve as important tools to gain mechanistic insight into salivary gland morphogenesis and diferentiation.

Comments

Publisher Acknowledgement:

This is the Publisher's PDF version. The version of record appears here:

Renee Thiemann, Deirdre Nelson, C. Michael DiPersio, Melinda Larsen, and Susan LaFlamme. 2019. Establishment of a Murine Pro-acinar Cell Line to Characterize Roles for FGF2 and α3β1 Integrins in Regulating Pro-acinar Characteristics. Scientific Reports. 9: 10984. doi: 10.1038/s41598-019-47387-y
PMCID: PMC6662831 PMID: 31358811

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