Background: Carcinomas are highly heterogeneous with regard to various cancer cells within a tumor microenvironment (TME), which is composed of stromal cells, blood vessels, immunocytes, and modified extracellular matrix. Focus of the study: Circular RNAs (circRNAs) are non-coding RNAs that are expressed in cancer and stromal cells. They are closely associated with cancer metastasis as their expression in tumor cells directs the latter to migrate to different organs. circRNAs packaged in exosomes might be involved in this process. This is particularly important as the TME acts in tandem with cancer cells to enhance their proliferation and metastatic capability. In this review, we focus on recent studies on the crosstalk between circRNAs and the TME during cancer metastasis. Conclusion: We particularly emphasize the roles of the interaction between circRNAs and the TME in anoikis resistance, vessel co-option, and local circRNA expression in directing homing of exosome.

Background: Primary ovarian mucinous tumors with mural nodules are very rare. The histogenesis of the mural nodules remains unclear. Methods: We investigated the clincopathological and molecular features in 3 cases with mural nodules. Results: Patient 1 was diagnosed as mucinous carcinoma with mural nodules of anaplastic carcinoma that was composed of CK+ and CK7+ spindled cells and polygonal cells with marked pleomorphism. Aberrant p53 staining was found in the mural nodules rather than in the mucinous components. A concordant KRAS mutation (c.35G > A p.G12A) was identified in both mucinous tumors and mural nodules. She died of disease at 44 months. The mural nodule in patient 2 was interpreted as a sarcoma, no other specified. The uniform short spindle cells were separated by abundant myxoid matrix. They were CD10 + , CCND1-, SMA-, and negative for break-apart BCOR, PHF1, and JAZF1 FISH assay. The adenocarcinomatous component harbored LOH at D18S51 and FGA loci while the sarcomatous component had LOH at D19S433. She had lung metastasis at 18 months and was alive without evidence of disease for 40 months. Patient 3 harbored multiple mural nodules that were composed of vimentin+, focal CK+, atypical spindle cells. A diagnosis of sarcoma-like mural nodules was rendered. She was alive with no evidence of disease for 13 months. No hotspot mutant AKT1, KRAS, HRAS, and PI3KCA alleles were found in patients 2 and 3. Conclusions: Mural nodules with anaplastic carcinoma or with true sarcomas may represent the dedifferentiation form of mucinous tumors or collision tumors, respectively. The worrisome histology in sarcoma-like mural nodules necessitates meticulous treatment for these patients.

Follicular dendritic cell secreted protein (FDCSP) is highly expressed in various cancers and has been implicated in tumor migration and invasion, yet its role in triple-negative breast cancer (TNBC) remains poorly understood. Our findings revealed that FDCSP expression was significantly elevated in TNBC compared to normal breast tissue, whereas its expression was significantly reduced in non-TNBC. In TNBC, high FDCSP expression was associated with an increased mutation rate of TP53 and influenced the infiltration of B cells and macrophages. Single-cell transcriptome analysis demonstrated that FDCSP was predominantly highly expressed in basal cells but exhibited low expression in luminal epithelial cells. This observation was further corroborated by spatial transcriptome (ST) analysis. Immunohistochemistry (IHC) assay also confirmed the distinct expression patterns of FDCSP. Cell-cell interaction and receptor-ligand pair analyses indicated that macrophages could interact with the receptor epidermal growth factor receptor (EGFR) in FDCSP highly expressed basal cells by secreting transforming growth factor-β1 (TGF-β1). Then, the co-localization of FDCSP and EGFR in TNBC basal cells was verified by IHC and immunofluorescence (IF) assay. Additionally, we discovered that FDCSP possesses strong predictive capabilities for distinguishing between responders and non-responders to Immune checkpoint blockade (ICB) treatment. Finally, leveraging the CARE database, we identified 14 potential FDCSP-related target drugs. These findings highlight the unique expression pattern of FDCSP in breast cancer, revealing FDCSP as a promising target for therapeutic strategies in TNBC.