Supplementary MaterialsTable S1: lists markers associated with CSC phenotype in ovarian cancer. and metastatic spread of disease. These studies describe a specific role for tissue-resident macrophages in the invasive progression of metastatic ovarian cancer. The molecular pathways of cross-talk between tissue-resident macrophages and disseminated cancer cells may represent new targets to prevent metastasis and disease recurrence. Graphical Abstract Open in a separate window Introduction Macrophages populate all human tissues, and their involvement in tumor progression and metastasis is well documented (Noy and Pollard, 2014). Recent advances in our understanding of macrophage biology suggest that tissue-resident macrophages and infiltrating tumor-associated macrophages (TAMs) display a high degree of heterogenity, in terms of both phenotype and ontogeny. However, our understanding of the physiological relevance of this heterogeneity and its implications for tumor development is still Vitexicarpin limited. In particular, Vitexicarpin the role of resident macrophages in tissue-specific tumor initiation and progression is unclear. Ovarian cancer is the eighth leading cause of cancer-related death in women worldwide and has a particularly poor prognosis due to almost 80% of cases being diagnosed with late-stage invasive disease (Ferlay et al., 2018). In particular, high-grade serous ovarian carcinoma (HGSOC), the most frequent and aggressive form of ovarian cancer, is characterized by the formation of Vitexicarpin malignant ascites and peritoneal metastases, which results in a disastrous prognosis (Lengyel, 2010). HGSOC originates from transformation of fallopian tube or ovarian surface epithelial cells that disseminate at early stages into the peritoneal cavity by exfoliation (Lengyel, 2010). Due to the lack of any anatomical barriers, exfoliated cancer cells are carried by the peritoneal fluid and spread throughout the abdominal cavity in a process termed transcolemic metastasis (Kipps et al., 2013). Several reports have also suggested that ovarian cancer cells in ascites acquire cancer stem cell (CSC)Clike properties that may play an important role in metastatic spread, chemosensitivity, and disease recurrence after therapy (Bapat et al., 2005). The most frequent site for metastasis in HGSOC is the omentum (Sehouli et al., 2009), an apron of visceral adipose tissue in the abdomen formed from a fold of the peritoneal mesothelium. Omentum contains a high density of lymphoid aggregates known as milky spots or fat-associated lymphoid COPB2 clusters (FALCs), which are thought to contribute to peritoneal and intestinal immunity (Krist et al., 1995; Rangel-Moreno et al., 2009; Bnzech et Vitexicarpin al., 2015). The tropism of ovarian cancer cells for the omentum and its implications for disease progression are not yet fully understood. Several reports have suggested that FALCs play an active role in colonization of omentum (Hagiwara et al., 1993), but the tumor-promoting function of FALCs was shown to be independent of both B and T lymphocytes (Clark et al., 2013). Myeloid cells are also abundant in FALCs, and macrophage denseness was recently proven to boost proportionally with disease rating in omenta from ovarian tumor individuals (Pearce et al., 2018). Nevertheless, the precise role of omental macrophages in disease and colonization progression continues to be to become explored. Tissue-resident macrophages perform trophic features that donate to body organ development, cells redesigning, and homeostasis (Pollard, 2009). Experimental proof shows that TAMs donate to tumor development by advertising angiogenesis, matrix redesigning, and epithelial-to-mesenchymal changeover (EMT; Raggi et al., 2016), which eventually leads to improved cell invasion and metastasis (Noy and Pollard, 2014). These properties reveal the trophic features of macrophages in advancement, and in keeping with these developmental features, the transcriptome of TAMs from mammary gland tumors offers been shown to become enriched for genes that also define embryonic macrophages (Ojalvo et al., 2010)..