Biology subjects

Khurram, S. A.

Publications and source records attributed to Khurram, S. A..

3 recordsLinked to original sources

bioRxiv2024

Hybrid cancer stem cells utilise vascular tracks for collective streaming invasion in a metastasis-on-a-chip device

Cancer stem cells (CSCs) drive cancer metastatic dissemination. They do not do so in a vacuum, and the important influence of the tumour microenvironment (TME) on metastatic dissemination is becoming increasingly recognised. Therapeutic targeting of CSC-TME interactions may be a promising route to suppression of tumour metastasis. However, we must first understand how interactions with the TME influence CSC metastatic dissemination. To achieve this understanding, there is a need for experimental models that enable the analysis of dynamic interactions at single cell resolution within a complex environment. To this end, we utilise a metastasis-on-a-chip device to produce a 3D in vitro model of CSC interaction with a developing microvasculature, that is amenable to precise imaging and real time studies at single cell resolution. We show that the invasive phenotype of oral squamous cell carcinoma (OSCC) cells is markedly altered when in proximity to a microvasculature, with a switch to a hybrid CSC phenotype that undergoes collective streaming invasion. Mechanistically, ECM compression by the developing vasculature creates an environment that is refractory to cancer invasion, whilst leaving abandoned vascular tracks that can be utilised by hybrid CSCs for collective streaming invasion. Human tissue studies identify streaming invasion in association with vascularised regions in OSCC specimens. These findings elucidate the influence of the vasculature on CSC metastatic dissemination in OSCC, and the role of hybrid CSC invasion plasticity in overcoming this TME constraint.

cancer biology↗

bioRxiv2022

Spatial transcriptome profiling of in vitro 3D tumouroids to study tumour-stroma interactions

Bioengineering facets of the tumour microenvironment (TME) are essential in 3D tissue models to accurately recapitulate tumour progression. Stromal cells are key components of the TME and their incorporation into 3D biomimetic bioengineered tumour-stroma models is essential to be able to mimic the TME. By engineering tumouroids with distinct tumour and stromal compartments, it has been possible to identify how gene expression is altered by the presence of different stromal cells using spatial transcriptomics. Ameloblastoma is a benign epithelial tumour of the jawbone and in engineered multi-compartment tumouroids increased expression of oncogenes was found where osteoblasts (bone stroma) were present. Engineering a gingival fibroblast stroma resulted in increased matrix remodelling genes in the ameloblastoma tumour. This study provides evidence to show the stromal specific effect on tumour behaviour and illustrates the importance of engineering biologically relevant stroma for engineered tumour models. Our novel results show that an engineered fibroblast stroma causes the upregulation of matrix remodelling genes in ameloblastoma which directly correlates to measured invasion in the model. In contrast the presence of an osteoblast/bone stroma increases the expression of oncogenes by ameloblastoma cells.

bioengineering↗

bioRxiv2022

Distribution and frequency of salivary gland tumours: an international multicenter study

BackgroundSalivary gland tumours (SGT) are a relatively rare group of neoplasms with a wide range of histopathological appearance and clinical features. To date, most of the epidemiological studies on salivary gland tumours are limited for a variety of reason including being out of date, extrapolated from either a single centre or country studies, or investigating either major or minor glands only. MethodsThis study aimed to mitigate these shortcomings by analysing epidemiological data including demographic, anatomical location and histological diagnoses of SGT from multiple centres across the world. The analysed data included age, gender, location and histological diagnosis from fifteen centres covering the majority of the world health organisation (WHO) geographical regions between 2006 and 2019. ResultsA total of 5798 cases were analysed including 65% benign and 35% malignant tumours. A slight female predilection (54%) and peak incidence between the fourth and seventh decade for both benign and malignant tumours was observed. The majority (69%) of the SGT presented in major and 31% in the minor glands. The parotid gland was the most common location (70%) for benign and minor glands (46%) for malignant tumours. Pleomorphic adenoma (70%), and Warthins tumour (17%), were the most common benign tumours whereas mucoepidermoid carcinoma (25%) and adenoid cystic carcinoma (16%) were the most frequent malignant tumours. ConclusionsThis multicentre investigation presents the largest cohort study to date analysing salivary gland tumour data from tertiary centres scattered across the globe. These findings should serve as a baseline for future studies evaluating the epidemiological landscape of these tumours.

pathology↗