| Periostin (Postn) is a secreted cell adhesion protein that shares a structural homology to the insect axon guidance protein fasciclin I (FAS1). Periostin interacts with multiple cell-surface receptors, most notably integrins, which activate signaling pathways to promote cancer cell survival, angiogenesis, invasion, and metastasis. Interestingly, periostin is frequently overexpressed in numerous human cancers, including breast, lung, colon, pancreatic, and ovarian cancer. Here, we investigated the role of periostin in HER2/ErbB2-induced mammary tumorigenesis. Although periostin is primarily expressed in the stromal fibroblasts and not the epithelial cells of the mammary gland, it does not affect mammary gland outgrowth during development or pregnancy when ablated. The male FVB Postn-/- mice were smaller than the male FVB Postn +/+ and Postn+/- mice, whereas there was no difference in size among the female mice of all genotypes. We also demonstrate that NeuNDL Postn+/- mice in a mixed FVB/C57 background (Postn +/-*) did not develop tumors after 12 months, whereas NeuNDL Postn+/- (Postn +/-) and NeuNDL Postn-/- (Postn -/-) mice in a pure FVB background developed tumors by 10 months of age, similar to NeuNDL Postn +/+ mice in a pure FVB background (Postn +/+). However, Postn +/+ tumors had a higher cellularity and appeared more dense than the cystic Postn +/- or Postn -/- tumors. In vitro studies with ErbB2/Neu overexpressing primary mammary tumor epithelial cells demonstrated that the presence of periostin does not affect the cell proliferation or migration rate. In conclusion, periostin ablation affects cellularity of NeuNDL tumors in vivo and may play a role in tumor cell proliferation in vivo. |
