Immunosuppressive traits of the hybrid epithelial/mesenchymal phenotype

Cancer metastasis remains a primary cause of cancer related mortality. Recent in vitro and in vivo data has indicated the high metastatic fitness of hybrid epithelial/mesenchymal (E/M) states, i.e. their enhanced abilities to initiate tumours at secondary tumour site. Mechanistic details about how such hybrid E/M cells survive the metastatic cascade remain unclear. Here, we investigate immune-evasive strategies of hybrid E/M states, an issue that to date has been largely unexplored. We construct a minimalistic regulatory network that captures known associations between regulators of EMT (the epithelial mesenchymal transition) and levels of PD-L1, an established suppressor of immune response, and simulated the network's emergent dynamics. Our model recapitulates observations that cells undergoing EMT have increased PD-L1 levels, while reverting EMT can decrease these levels, indicative of a causal link between EMT drivers and PD-L1. Further, we show that hybrid E/M cells can have high levels of PD-L1, similar to those seen in cells with a full EMT phenotype, thus obviating the need for cancer cells to undergo a full EMT to evade the immune system. Finally, we identify various signalling pathways and cellular processes that can independently or in concert affect PD-L1 levels and EMT status. For instance, hybrid E/M cells can gain both immune-evasion and stemness through largely independent paths. Our results underscore another underlying reason for the high metastatic ability of hybrid E/M cells.

Prostate Cancer Cell Extracellular Vesicles Increase Mineralisation of Bone Osteoblast Precursor Cells in an In Vitro Model

Skeletal metastases are the most common form of secondary tumour associated with prostate cancer (PCa). The aberrant function of bone cells neighbouring these tumours leads to the devel-opment of osteoblastic lesions. Communication between PCa cells and bone cells in bone envi-ronments governs both the formation/development of the associated lesion, and growth of the secondary tumour. Using osteoblasts as a model system, we observed that PCa cells and their conditioned medium could stimulate and increase mineralisation and osteoblasts’ differentiation. Secreted factors within PCa-conditioned medium responsible for osteoblastic changes included small extracellular vesicles (sEVs), which were sufficient to drive osteoblastogenesis. Using MiR-seq, we profiled the miRNA content of PCa sEVs, showing that miR-16-5p was highly ex-pressed. MiR-16 was subsequently higher in EV-treated 7F2 cells and a miR-16 mimic could also stimulate mineralisation. Next, using RNA-seq of extracellular vesicle (EV)-treated 7F2 cells, we observed a large degree of gene downregulation and an increased mineralisation. Ingenuity® Pathway Analysis (IPA®) revealed that miR-16-5p (and other miRs) was a likely upstream effec-tor. MiR-16-5p targets in 7F2 cells, possibly involved in osteoblastogenesis, were included for val-idation, namely AXIN2, PLSCR4, ADRB2 and DLL1. We then confirmed the targeting and dow-regulation of these genes by sEV miR-16-5p using luciferase UTR (untranslated region) reporters. Conversely, the overexpression of PLSCR4, ADRB2 and DLL1 lead to decreased osteoblastogene-sis. These results indicate that miR-16 is an inducer of osteoblastogenesis and is transmitted through prostate cancer-derived sEVs. The mechanism is a likely contributor towards the for-mation of osteoblastic lesions in metastatic PCa.

Radiogenic Vaginal Angiosarcoma: a Clinical Case

Background. Vaginal sarcomas are rare malignant mesenchymal neoplasms. Incidence rate of vulvar and vaginal sarcomas ranges from 1 to 3%. Vaginal sarcomas are usually represented by leiomyosarcomas in reproductive-age women. More seldom are soft tissue fibrosarcomas, angiosarcomas, malignant fi brous histiocytomas and alveolar soft tissue sarcomas. Tumours induced by prior radiation therapy deserve special concern. In oncogynaecology, radiation therapy is commonly applied in cervical and endometrial cancer therapy. According to some evidence, average development time of a secondary tumour after completion of radiation therapy is 10.8 years. The relative risk of vaginal cancer increases by a factor of 300 after radiation therapy.Materials and methods. The reported clinical case represents a rare vaginal tumour, angiosarcoma, developed 26 years after radiation therapy for gynaecological cancer.Results and discussion. A 78 years-old patient underwent combined tumourectomy of the posterior vaginal wall with resection of the anterior rectal wall and application of preventive transversostoma. No postoperative complications were observed.Conclusion. Surgical treatment is a method of choice with patients of such kind and allows local containment of the disease.

The Characteristic of Secondary Lung Tumours in Medan

BACKGROUND: Metastatic malignant neoplasms are the most commonly known as secondary lung tumour. Any cancer could have the ability to spread to the lung. The secondary tumour most typically appears on radiologic findings are multiple nodules pleural effusion, etc. AIM: To observe the characteristic of secondary lung tumours patients in Haji Adam Malik General Hospital. MATERIAL AND METHODS: Research design is a cross-sectional with consecutive sampling to 53 patients that are diagnosed with secondary lung tumours. The data was taken from the medical record of secondary lung tumours diagnoses in Haji Adam Malik General Hospital medical record department. RESULTS: From the study, most cases are found in < 40-year-old age group with a percentage of 34%. The highest secondary lung tumour was ovarian carcinoma (13.2%) and multiple nodules (52.8%) from radiology images. Adenocarcinoma is the most found cytology/histopathology type which is around 69.8%. CONCLUSION: Female ages < 40 years are the group with the most cases of secondary lung tumours. Primary tumour from the ovarian is the main cause of secondary lung tumour.

Ampelopsin E Reduces the Invasiveness of the Triple Negative Breast Cancer Cell Line, MDA-MB-231

Breast cancer is the most common and the second leading cause of cancer-related deaths in women. It has two distinctive hallmarks: rapid abnormal growth and the ability to invade and metastasize. During metastasis, cancer cells are thought to form actin-rich protrusions, called invadopodia, which degrade the extracellular matrix. Current breast cancer treatments, particularly chemotherapy, comes with adverse effects like immunosuppression, resistance development and secondary tumour formation. Hence, naturally-occurring molecules claimed to be less toxic are being studied as new drug candidates. Ampelopsin E, a natural oligostilbene extracted from Dryobalanops species, has exhibited various pharmacological properties, including anticancer and anti-inflammatory activities. However, there is yet no scientific evidence of the effects of ampelopsin E towards metastasis. Scratch assay, transwell migration and invasion assays, invadopodia and gelatin degradation assays, and ELISA were used to determine the effects of ampelopsin E towards the invasiveness of MDA-MB-231 cells. Strikingly in this study, ampelopsin E was able to halt migration, transmigration and invasion in MDA-MB-231 cells by reducing formation of invadopodia and its degradation capability through significant reduction (p < 0.05) in expression levels of PDGF, MMP2, MMP9 and MMP14. In conclusion, ampelopsin E reduced the invasiveness of MDA-MB-231 cells and was proven to be a potential alternative in treating TNBC.

Label-free identification and characterization of living human primary and secondary tumour cells

Primary and secondary tumour cells exhibit biochemical differences (with Raman spectroscopy and imaging), and mechanical differences (with atomic force microscopy).

Phosphorylation of basic helix–loop–helix transcription factor Twist in development and disease

The transcription factor Twist plays vital roles during embryonic development through regulating/controlling cell migration. However, postnatally, in normal physiological settings, Twist is either not expressed or inactivated. Increasing evidence shows a strong correlation between Twist reactivation and both cancer progression and malignancy, where the transcriptional activities of Twist support cancer cells to disseminate from primary tumours and subsequently establish a secondary tumour growth in distant organs. However, it is largely unclear how this signalling programme is reactivated or what signalling pathways regulate its activity. The present review discusses recent advances in Twist regulation and activity, with a focus on phosphorylation-dependent Twist activity, potential upstream kinases and the contribution of these factors in transducing biological signals from upstream signalling complexes. The recent advances in these areas have shed new light on how phosphorylation-dependent regulation of the Twist proteins promotes or suppresses Twist activity, leading to differential regulation of Twist transcriptional targets and thereby influencing cell fate.