Peritoneal metastases are the leading cause of morbidity and mortality in high-grade serous ovarian cancer (HGSOC). Accumulating evidence suggests that mesothelial cells are an important component of the metastatic microenvironment in HGSOC. However, the mechanisms by which mesothelial cells promote metastasis are unclear. Here we report that the HGSOC tumor-mesothelial niche was hypoxic and hypoxic signaling enhanced collagen I deposition by mesothelial cells. Specifically, hypoxic signaling increased expression of lysyl oxidase (LOX) in mesothelial and ovarian cancer cells to promote collagen crosslinking and tumor cell invasion. The mesothelial niche was enriched with fibrillar collagen in human and murine omental metastases. Pharmacologic inhibition of LOX reduced tumor burden and collagen remodeling in murine omental metastases. These findings highlight an important role for hypoxia and mesothelial cells in the modification of the extracellular matrix and tumor invasion in HGSOC.

Studies investigating the brain in relation to religious experiences via neuroimaging tools have increased considerably. Most assume without verification that religious experience (e.g., prayer) while inside an imaging machine is the same as in normal settings. Addressing the validity of this assumption, we utilized a mock fMRI to compare self-reported typical prayer experience and 3 experimental conditions (silent room, initial fMRI, and acclimated fMRI). Forty-two individuals participated. In multiple aspects the "typical" and silent room conditions were indistinguishable; however, typical and fMRI conditions differed significantly. In sum, it was not clear what previous studies measured. These findings highlight the need for imaging research exploring religious experiences to include thorough debriefing protocols to disambiguate interpretations and facilitate meta-analytic efforts.

<p>Supplementary Table S2 shows the list of overlapping genes between the metastatic and hypoxic gene signatures. Suppl. to Fig 1.</p>

<p>Supplementary Table S3 shows the list of primer sequences of forward and reverse human primer sets used for real time qPCR in the study. Suppl. to Materials and Methods</p>

<p>Supplementary Table S1 shows the list of genes upregulated in metastasis verus matched primary HGSOC. Suppl. to Fig 1.</p>