Dataset Information

Quantitative LC-MS/MS Proteomics of human small intestine

ABSTRACT: The objective was to determine the expression of a wide range proteins pertinent to metabolism and disposition of chemicals and nutrients in the intestinal epithelium. Ileum and jejunum biopsy specimens were obtained from 16 patients undergoing gastrointestinal elective surgery. Mucosal fractions were prepared and analysed using targeted and global proteomic approaches. A total of 29 enzymes, 32 transporters, 6 tight junction proteins, 2 adhesion proteins, alkaline phosphatase, thioredoxin, 5 markers and 1 regulatory protein were quantified; 60 for the first time.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Small Intestine Mucosa

SUBMITTER: Jill Barber

LAB HEAD: Jill Barber

PROVIDER: PXD020987 | Pride | 2021-09-09

REPOSITORIES: Pride

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Publications

Mass spectrometry-based abundance atlas of ABC transporters in human liver, gut, kidney, brain and skin.

Al-Majdoub Zubida M ZM Achour Brahim B Couto Narciso N Howard Martyn M Elmorsi Yasmine Y Scotcher Daniel D Alrubia Sarah S El-Khateeb Eman E Vasilogianni Areti-Maria AM Alohali Noura N Neuhoff Sibylle S Schmitt Lutz L Rostami-Hodjegan Amin A Barber Jill J

FEBS letters 20201203 23

ABC transporters (ATP-binding cassette transporter) traffic drugs and their metabolites across membranes, making ABC transporter expression levels a key factor regulating local drug concentrations in different tissues and individuals. Yet, quantification of ABC transporters remains challenging because they are large and low-abundance transmembrane proteins. Here, we analysed 200 samples of crude and membrane-enriched fractions from human liver, kidney, intestine, brain microvessels and skin, by ...[more]

PMID: 33128234

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Project description:The cellular heterogeneity of one patient derived orthotopic breast cancer xenograft model (PDBCX) was investigated using flow cytometry , combined with assessment of in vivo tumorigenicity and whole genome expression profiling. Epithelial cell adhesion molecule (EpCAM) was revealed as a highly specific cell surface marker of the human tumor cell population in both xenografts. Based on expression patterns observed in primary tumor tissue, SSEA-4 and CD24 were chosen as markers to further subdivide the luminal tumor cells into four subpopulations. FACS sorting was used to isolate four cell subpopulations. Results: In vivo tumorigenicity assay showed that SSEA-4+/CD24+ cells were non-tumorigenic, while the three other subpopulations were tumorigenic. Tumors resulting from the SSEA-4+/CD24- subpopulation of luminal cancer cells, did not express CD24, while tumors arising from the SSEA-4-/CD24-, and SSEA-4-/CD24+ populations both recapitulated the original tumor containing all four subpopulations. Whole genome expression analysis revealed distinct transcriptional profiles, and 44 genes were significantly differentially expressed when comparing the tumorigenic vs non-tumorigenic populations. Several interesting genes putatively suppressing the cancer cells ability to initiate tumors in vivo were upregulated in the non-tumorigenic population. We here show that tumor initiating cells within one primary tumor evidently included more than one phenotype. Furthermore, with respect to cell surface marker expression, one of the subpopulations produced tumors unlike both the originating cells, and the original tumor. Discussion: Our results imply that subpopulations from one primary tumor can give rise to dissimilar daughter tumors. These tumors may not necessarily respond to the same targeted treatment, and thereby represent a therapy escape mechanism. This study highlights that to remove the risk of breast cancer recurrence, inhibition of the molecules critical for driving the tumor progression in several tumor cell subpopulations might be essential Gene expression was measured in four cell subpopulations isolated from Patient derived human luminal-like breast cancer xenograft. Four replicates from three subpopulations and three replicates from one subpopulation.

Dataset Information

Quantitative LC-MS/MS Proteomics of human small intestine

Publications

Mass spectrometry-based abundance atlas of ABC transporters in human liver, gut, kidney, brain and skin.

Similar Datasets

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