PXD044297

PXD044297 is an original dataset announced via ProteomeXchange.

Title	Hybrid Epithelial-Mesenchymal status of lung cancer dictates metastatic success through differential interaction with NK cells
Description	Background Epithelial to mesenchymal transition (EMT) endows cancer cells with pro-metastatic properties, which appear most effective when cells enter an intermediate hybrid (H) state, characterized by integrated mesenchymal (M) and epithelial (E) traits. The reasons for this advantage are poorly known and, especially, it is totally unexplored whether the interplay between H-cells and NK cells could have a role. Here we characterize the pro-metastatic mechanics of Non-small Cell Lung Cancer (NSCLC) H-cells and their subset of cancer-initiating cells (CICs), dissecting crucial interactions with NK cells. Methods Human lung cancer cell lines and sub-lines representative of E, M, or H states, assessed by proteomics, were analysed in vivo for their tumor-forming and disseminating capabilities. Interactions with NK cells were investigated in vitro using migration assays, cytotoxic degranulation assays and evaluation of CD133+ CICs modulation after co-culture, and validated in vivo through NK cell neutralization assays. Correlation between EMT status, NK cell infiltration, and survival data, was evaluated in a cohort of surgically resected NSCLC cases (n=79). Results We demonstrated that H-cells, have limited dissemination capability but show highest potential to initiate metastases in vivo. This property was related to their ability to escape NK cell surveillance. Mechanistically, H-cells expressed low levels of NK-attracting chemokines (CXCL1 and CXCL8), generating poorly infiltrated metastases. Accordingly, proteomics and GO enrichment analysis of E, H, M cell lines showed that the related secretory processes could change during EMT. Furthermore, H-CICs uniquely expressed high levels of the inhibitory ligand B7-H3, which protected H-CIC from NK cell-mediated clearance. In vivo neutralization assays confirmed that, indeed, the pro-metastatic properties of H-cells are poorly controlled by NK cells. Finally, the analysis of patients revealed that detection of hybrid phenotypes associated with low NK infiltration in NSCLC clinical specimens could identify a subset of patients with poor prognosis. Conclusions Our study demonstrates that H-cells play a central role in the metastatic spread in NSCLC. Such pro-metastatic advantage of H-cells is supported by their altered interaction with NK cells and by the critical role of B7H3 in preserving their H-CIC component, indicating B7H3 as a potential target in combined NK-based therapies.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:40:43.527.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Martina Bartolucci
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-02 05:09:25	ID requested
1	2024-05-21 13:21:24	announced
⏵ 2	2024-10-22 06:40:44	announced	2024-10-22: Updated project metadata.

Parodi M, Centonze G, Murianni F, Orecchia P, Andriani F, Roato I, Gardelli C, Balsamo M, Moro M, Tai, è G, Pastorino U, Petretto A, Lavarello C, Milione M, Sozzi G, Roz L, Vitale M, Bertolini G, Hybrid epithelial-mesenchymal status of lung cancer dictates metastatic success through differential interaction with NK cells. J Immunother Cancer, 12(3):(2024) [pubmed]

10.1136/jitc-2023-007895;

submitter keyword: Cancer Initiating Cell, proteomics, mass spectrometry, Natural killer, Epithelial-to-Mesenchymal Transition

Andrea Petretto
contact affiliation	IRCCS Istituto G Gaslini
contact email	a.petretto@gmail.com
lab head
Martina Bartolucci
contact affiliation	IRCCS Gaslini
contact email	smartibartolucci@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044297
     1. Label: PRIDE project
     2. Name: Hybrid Epithelial-Mesenchymal status of lung cancer dictates metastatic success through differential interaction with NK cells