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Latent TGFβ binding proteins (LTBPs) govern TGFβ presentation and activation and are important for elastogenesis. Although TGFβ is well-known as a tumor suppressor and metastasis promoter, and LTBP1 is elevated in two distinct breast cancer metastasis signatures, LTBPs have not been studied in the normal mammary gland.    Methods  To address this we have examined  Ltbp1  promoter activity throughout mammary development using an Ltbp1L-LacZ reporter as well as expression of both Ltbp1L and 1S mRNA and protein by qRT-PCR, immunofluorescence and flow cytometry.    Results  Our data show that  Ltbp1L  is transcribed coincident with lumen formation, providing a rare marker distinguishing ductal from alveolar luminal lineages.  Ltbp1L  and  Ltbp1S  are silent during lactation but robustly induced during involution, peaking at the stage when the remodeling process becomes irreversible.  Ltbp1L  is also induced within the embryonic mammary mesenchyme and maintained within nipple smooth muscle cells and myofibroblasts. Ltbp1 protein exclusively ensheaths ducts and side branches.    Conclusions  These data show  Ltbp1  is transcriptionally regulated in a dynamic manner that is likely to impose significant spatial restriction on TGFβ bioavailability during mammary development. We hypothesize that Ltbp1 functions in a mechanosensory capacity to establish and maintain ductal luminal cell fate, support and detect ductal distension, trigger irreversible involution, and facilitate nipple sphincter function.

Ltbp1Lis focally induced in embryonic mammary mesenchyme, demarcates the ductal luminal lineage and is upregulated during involution