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A journey to uncharted territory: new technical frontiers in studying tumor-stromal cell interactions.

ABSTRACT: The crosstalk between tumor cells and cells of the tumor stroma dictate malignant progression and represent an intriguing and viable anticancer therapeutic target. The successful development of therapeutics targeting tumor-stroma interactions is tied to the insight provided by basic research on such crosstalk. Tumor-stroma interactions can be transient and dynamic, and they occur within defined spatiotemporal contexts among genetically and compositionally heterogeneous populations of cells, yet methods currently applied to study the said crosstalk do not sufficiently address these features. Emerging imaging and genetic methods, however, can overcome limitations of traditional approaches and provide unprecedented insight into tumor-stroma crosstalk with unparalleled accuracy. The comprehensive data obtained by applying emerging methods will require processing and analysis by multidisciplinary teams, but the efforts will ultimately rejuvenate hope in developing novel therapies against pro-tumorigenic tumor-stroma crosstalk.

SUBMITTER: Guldner IH

PROVIDER: S-EPMC4324098 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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A journey to uncharted territory: new technical frontiers in studying tumor-stromal cell interactions.

Guldner Ian H IH Zhang Siyuan S

Integrative biology : quantitative biosciences from nano to macro 20150201 2

The crosstalk between tumor cells and cells of the tumor stroma dictate malignant progression and represent an intriguing and viable anticancer therapeutic target. The successful development of therapeutics targeting tumor-stroma interactions is tied to the insight provided by basic research on such crosstalk. Tumor-stroma interactions can be transient and dynamic, and they occur within defined spatiotemporal contexts among genetically and compositionally heterogeneous populations of cells, yet ...[more]

PMID: 25500646

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Project description:INTRODUCTION:Cutaneous leishmaniasis (CL) is the most frequent form of leishmaniasis, with 0.7 to 1.2 million cases per year globally. However, the burden of CL is poorly documented in some regions. We carried out this review to synthesize knowledge on the epidemiological burden of CL in sub-Saharan Africa. METHODS:We systematically searched PubMed, CABI Global health, Africa Index Medicus databases for publications on CL and its burden. There were no restrictions on language/publication date. Case series with less than ten patients, species identification studies, reviews, non-human, and non-CL focused studies were excluded. Findings were extracted and described. The review was conducted following PRISMA guidelines; the protocol was registered in PROSPERO (42016036272). RESULTS:From 289 identified records, 54 met eligibility criteria and were included in the synthesis. CL was reported from 13 of the 48 sub-Saharan African countries (3 eastern, nine western and one from southern Africa). More than half of the records (30/54; 56%) were from western Africa, notably Senegal, Burkina Faso and Mali. All studies were observational: 29 were descriptive case series (total 13,257 cases), and 24 followed a cross-sectional design. The majority (78%) of the studies were carried out before the year 2000. Forty-two studies mentioned the parasite species, but was either assumed or attributed on the historical account. Regional differences in clinical manifestations were reported. We found high variability across methodologies, leading to difficulties to compare or combine data. The prevalence in hospital settings among suspected cases ranged between 0.1 and 14.2%. At the community level, CL prevalence varied widely between studies. Outbreaks of thousands of cases occurred in Ethiopia, Ghana, and Sudan. Polymorphism of CL in HIV-infected people is a concern. Key information gaps in CL burden here include population-based CL prevalence/incidence, risk factors, and its socio-economic burden. CONCLUSION:The evidence on CL epidemiology in sub-Saharan Africa is scanty. The CL frequency and severity are poorly identified. There is a need for population-based studies to define the CL burden better. Endemic countries should consider research and action to improve burden estimation and essential control measures including diagnosis and treatment capacity.

Project description:Considerable evidence suggests that cancer stem-like cells (CSCs) are critical in tumor pathogenesis, but their rarity and transience has led to much controversy about their exact nature. Although CSCs can be functionally identified using dish-based tumorsphere assays, it is difficult to handle and monitor single cells in dish-based approaches; single cell-based microfluidic approaches offer better control and reliable single cell derived sphere formation. However, like normal stem cells, CSCs are heavily regulated by their microenvironment, requiring tumor-stromal interactions for tumorigenic and proliferative behaviors. To enable single cell derived tumorsphere formation within a stromal microenvironment, we present a dual adherent/suspension co-culture device, which combines a suspension environment for single-cell tumorsphere assays and an adherent environment for co-culturing stromal cells in close proximity by selectively patterning polyHEMA in indented microwells. By minimizing dead volume and improving cell capture efficiency, the presented platform allows for the use of small numbers of cells (<100 cells). As a proof of concept, we co-cultured single T47D (breast cancer) cells and primary cancer associated fibroblasts (CAF) on-chip for 14 days to monitor sphere formation and growth. Compared to mono-culture, co-cultured T47D have higher tumorigenic potential (sphere formation rate) and proliferation rates (larger sphere size). Furthermore, 96-multiplexed single-cell transcriptome analyses were performed to compare the gene expression of co-cultured and mono-cultured T47D cells. Phenotypic changes observed in co-culture correlated with expression changes in genes associated with proliferation, apoptotic suppression, tumorigenicity and even epithelial-to-mesechymal transition. Combining the presented platform with single cell transcriptome analysis, we successfully identified functional CSCs and investigated the phenotypic and transcriptome effects induced by tumor-stromal interactions.

Dataset Information

A journey to uncharted territory: new technical frontiers in studying tumor-stromal cell interactions.

Publications

A journey to uncharted territory: new technical frontiers in studying tumor-stromal cell interactions.

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