PXD000682-1

PXD000682 is an original dataset announced via ProteomeXchange.

Title	Transcriptomic and Proteomic Response of HC-04 to hepatocyte growth factor (HGF)
Description	The routine study of human malaria liver-stage biology in vitro is hampered by low infection efficiency of human hepatocellular carcinoma (HCC) lines (<0.1%), poor understanding of steady-state HCC biology, and lack of appropriate tools for trace sample analysis. HC-04 is the only HCC that supports complete development of human malaria parasites. We hypothesized that HCCs are in various intermediate stages of the epithelial-mesenchymal transition (EMT) and HC-04s retain epithelial characteristics that permit infection. We developed an novel analytical approach to test this hypothesis viz. the HC-04 response to hepatocyte growth factor (HGF). We used online two-dimensional liquid chromatography tandem mass spectrometry (2D-LC-MS/MS) to quantify protein expression profiles in HC-04 pre-/post-HGF treatment and validated these results by RT-qPCR and microscopy. We successfully increased protein identification efficiency over offline-2D methods by 12-fold using less sample material, allowing robust protein quantification. We observed expected up-regulation and down-regulation of EMT protein markers in response to HGF, but also unexpected cellular responses. HC-04 is thus susceptible to HGF-mediated signaling but to a lesser degree than what we observed for HepG2, a widely used, but poor malaria HCC model. Our analytical approach to understanding the basic biology of HC-04 helps us understand the factors that may influence its utility as a model for malaria liver-stage development. We observed that HC-04 treatment with HGF prior to the addition of Plasmodium falciparum sporozoites did not facilitate cell invasion, arguing for unlinking the effect of HGF on malaria liver stage development from hepatocyte invasion. Finally, our 2D-LC-MS/MS approach and broadly applicable experimental strategy should prove useful in the analysis of various hepatocyte-pathogen interactions, tumor progression and early disease events.
HostingRepository	PRIDE
AnnounceDate	2014-02-18
AnnouncementXML	Submission_2014-02-18_03:22:10.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD000682
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Dingyin Tao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Oxidation; Carbamidomethyl
Instrument	6520 Quadrupole Time-of-Flight LC/MS

Revision	Datetime	Status	ChangeLog Entry
0	2014-01-14 01:52:25	ID requested
⏵ 1	2014-02-18 03:22:11	announced
2	2014-07-24 03:49:01	announced	Updated project metadata.

Tao D, King JG, Tweedell RE, Jost PJ, Boddey JA, Dinglasan RR, The acute transcriptomic and proteomic response of HC-04 hepatoma cells to hepatocyte growth factor and its implications for Plasmodium falciparum sporozoite invasion. Mol Cell Proteomics, 13(5):1153-64(2014) [pubmed]

submitter keyword: Human Hepatocellular carcinoma, EMT, Malaria, Host-Pathogen Interaction, Transcriptomics, Proteomics, Mass Spectrometry

Rhoel R. Dinglasan
contact affiliation	W. Harry Feinstone Department of Molecular Microbiology & Immunology and the Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health
contact email	rdinglas@jhsph.edu
lab head
Dingyin Tao
contact affiliation	W. Harry Feinstone Department of Molecular Microbiology & Immunology
contact email	dtao@jhsph.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD000682
     1. Label: PRIDE project
     2. Name: Transcriptomic and Proteomic Response of HC-04 to hepatocyte growth factor (HGF)