TACSTD2 upregulation is an early reaction to lung infection

Abstract

TACSTD2 encodes a transmembrane glycoprotein Trop2 commonly overexpressed in carcinomas. While the Trop2 protein was discovered already in 1981 and first antibody–drug conjugate targeting Trop2 were recently approved for cancer therapy, the physiological role of Trop2 is still not fully understood. In this article, we show that TACSTD2/Trop2 expression is evolutionarily conserved in lungs of various vertebrates. By analysis of publicly available transcriptomic data we demonstrate that TACSTD2 level consistently increases in lungs infected with miscellaneous, but mainly viral pathogens. Single cell and subpopulation based transcriptomic data revealed that the major source of TACSTD2 transcript are lung epithelial cells and their progenitors and that TACSTD2 is induced directly in lung epithelial cells following infection. Increase in TACSTD2 expression may represent a mechanism to maintain/restore epithelial barrier function and contribute to regeneration process in infected/damaged lungs.

Development of a new flippase-dependent mouse model for red fluorescence-based isolation of KrasG12Doncogene-expressing tumor cells

“…This antigen is highly expressed in most carcinomas, where it is associated with increased invasiveness and metastasis. In addition, Trop2 is expressed in the lungs of various organisms; in mice, Trop is mainly produced in the airway epithelium (Lenart et al 2022). Our staining with an anti-Trop2 antibody confirmed this.…”

Distinctive transcriptomic and epigenomic signatures of bone marrow-derived myeloid cells and microglia in CNS autoimmunity

“…Notably, the literature ascribes immunomodulatory roles for coagulation factors released by macrophages in antitumor immunity and bacterial infection ( 44 , 45 ). Chromatin accessibility at loci overlapping with the cds of genes Pdpn [a transmembrane glycoprotein promoting angiogenesis and motility ( 46 , 47 )], Tacstd2 [a transmembrane glycoprotein linked to tissue regeneration and cancer proliferation ( 48 , 49 )], and Nrg4 [which encodes for the ErbB4 ligand neuregulin-4 that appears to function in feedback control of activated macrophages ( 50 )] were also enriched in BMC. However, differential gene expression of these genes was only modestly increased in this cell population relative to microglia.…”