Breast manifestation of extramedullary myeloid sarcoma: A case report.

Extramedullary myeloid sarcoma (MS) of the breast is a rare disease, representing 0.12% of all diagnoses of acute myeloid leukemia. We review a case of a 27-year-old female who presented with a palpable right breast mass. She subsequently underwent a biopsy, which showed breast tissue with diffuse infiltrate of blasts compatible with MS. A bone marrow biopsy was performed with no evidence of leukemia or lymphoma. Therefore, a second breast biopsy was obtained for additional testing and cytogenetics which demonstrated positive (t8;21)(q22;q22) translocation associated with acute myeloid leukemia. Patient was admitted for induction of chemotherapy, but she subsequently developed neutropenic colitis and C. diff colitis. Unfortunately, her condition quickly deteriorated, and she passed away shortly after. This report aims to describe the clinical, radiographic, and pathological features of a case of extramedullary MS involving the breast.

Small extracellular vesicles modulated by αVß3 integrin induce neuroendocrine differentiation in recipient cancer cells.

The ability of small extracellular vesicles (sEVs) to reprogram cancer cells is well established. However, the specific sEV components able to mediate aberrant effects in cancer cells have not been characterized. Integrins are major players in mediating sEV functions. We have previously reported that the αVß3 integrin is detected in sEVs of prostate cancer (PrCa) cells and transferred into recipient cells. Here, we investigate whether sEVs from αVß3-expressing cells affect tumour growth differently than sEVs from control cells that do not express αVß3. We compared the ability of sEVs to stimulate tumour growth, using sEVs isolated from PrCa C4-2B cells by iodixanol density gradient and characterized with immunoblotting, nanoparticle tracking analysis, immunocapturing and single vesicle analysis. We incubated PrCa cells with sEVs and injected them subcutaneously into nude mice to measure in vivo tumour growth or analysed in vitro their anchorage-independent growth. Our results demonstrate that a single treatment with sEVs shed from C4-2B cells that express αVß3, but not from control cells, stimulates tumour growth and induces differentiation of PrCa cells towards a neuroendocrine phenotype, as quantified by increased levels of neuroendocrine markers. In conclusion, the expression of αVß3 integrin generates sEVs capable of reprogramming cells towards an aggressive phenotype.

The αvß6 integrin in cancer cell-derived small extracellular vesicles enhances angiogenesis.

Prostate cancer (PrCa) cells crosstalk with the tumour microenvironment by releasing small extracellular vesicles (sEVs). sEVs, as well as large extracellular vesicles (LEVs), isolated via iodixanol density gradients from PrCa cell culture media, express the epithelial-specific αvß6 integrin, which is known to be induced in cancer. In this study, we show sEV-mediated protein transfer of αvß6 integrin to microvascular endothelial cells (human microvascular endothelial cells 1 - HMEC1) and demonstrate that de novo αvß6 integrin expression is not caused by increased mRNA levels. Incubation of HMEC1 with sEVs isolated from PrCa PC3 cells that express the αvß6 integrin results in a highly significant increase in the number of nodes, junctions and tubules. In contrast, incubation of HMEC1 with sEVs isolated from ß6 negative PC3 cells, generated by shRNA against ß6, results in a reduction in the number of nodes, junctions and tubules, a decrease in survivin levels and an increase in a negative regulator of angiogenesis, pSTAT1. Furthermore, treatment of HMEC1 with sEVs generated by CRISPR/Cas9-mediated down-regulation of ß6, causes up-regulation of pSTAT1. Overall, our findings suggest that αvß6 integrin in cancer sEVs regulates angiogenesis during PrCa progression.

Tumor-Derived Extracellular Vesicles Require ß1 Integrins to Promote Anchorage-Independent Growth.

The ß1 integrins, known to promote cancer progression, are abundant in extracellular vesicles (EVs). We investigated whether prostate cancer (PrCa) EVs affect anchorage-independent growth and whether ß1 integrins are required for this effect. Specifically using a cell-line-based genetic rescue and an in vivo PrCa model, we show that gradient-purified small EVs (sEVs) from either cancer cells or blood from tumor-bearing TRAMP (transgenic adenocarcinoma of the mouse prostate) mice promote anchorage-independent growth of PrCa cells. In contrast, sEVs from cultured PrCa cells harboring a short hairpin RNA to ß1, from wild-type mice or from TRAMP mice carrying a ß1 conditional ablation in the prostatic epithelium (ß1pc-/-), do not. We find that sEVs, from cancer cells or TRAMP blood, are functional and co-express ß1 and sEV markers; in contrast, sEVs from ß1pc-/-/TRAMP or wild-type mice lack ß1 and sEV markers. Our results demonstrate that ß1 integrins in tumor-cell-derived sEVs are required for stimulation of anchorage-independent growth.