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Cancer Research using Label-Free MALDI Imaging

Cancer Research using Label-Free MALDI Imaging

Publication Key Features
Research Focus
MALDI Mass Spectrometry Imaging Linked with Top-Down Proteomics as a Tool to Study the Non-Small-Cell Lung Cancer Tumor Microenvironment.
Berghmans E, et al., Methods and Protocols, (2019)
DOI: 10.3390/mps2020044  
Cancer biology: Non-small-cell lung carcinoma (NSCLC) targeting proteins and peptides.
Bruker product: rapfleX MALDI/TOF-TOF with SCiLS Lab analytical software suite.
Sample: Human resected tumor.  
Combined MALDI Imaging and LC-MS proteomics to elucidate the basic cancer biology and protein profiles of NSCLC.
MALDI Imaging highlighted significant peptide compounds localized in either tumor and non-tumor, complemented by top-down proteomics identification to provide a comprehensive molecular profile of tumor/non-tumor cells.
Rapid discrimination of pediatric brain tumors by mass spectrometry imaging.
Clark AR, et al., Journal of Neuro-Oncology, (2018).
DOI: 10.1007/s11060-018-2978-2
Tissue typing: Differentiating blastomas pathology targeting lipids.
Bruker product: solarix MRMS with SCiLS Lab analytical software suite.
Sample: Human tumor of blastomas.
Histopathological similarities between medulloblastoma and pineoblastoma make traditional pathological classification methods difficult.
MALDI Imaging reveal the distinctive lipid mass profiles of medulloblastoma and pineoblastoma, allowing robust statistical classification. This provides an accurate, objective way for pathologists to distinguish between the two blastomas.
Mass spectrometry imaging of the in situ drug release from nanocarriers.
Xue J, et al., Science Advances, (2018).
DOI: 10.1126/sciadv.aat9039   
Chemotherapeutics: pharmacokinetics of drugs loaded onto nanocarriers targeting drug compounds.
Bruker product: ultrafleXtreme MALDI/TOF-TOF.
Sample: Tumors from mice derived from cell lines H22 (liver) and 4T1 (breast).  
Using nanocarrier Molybdenum disulfide (MoS2) nanosheets loaded with doxorubicin (DOX) to target release into tumor cells.
MALDI Imaging shows that MoS2 successfully accumulated in lung, spleen and liver but release of DOX within tumors remained low, pointing to pharmacokinetics resistance of nanocarrier based drug delivery.
Mass Spectrometry Imaging Reveals Neutrophil Defensins as Additional Biomarkers for Anti-PD-(L)1 Immunotherapy Response in NSCLC Patients
Berghmans E, et al., Cancers, (2020).
DOI:10.3390/cancers12040863  
Immunotherapy: biomarkers to improve efficacy determination targeting small proteins.
Bruker product: rapifleX MALDI/TOF-TOF.
Sample: Human tumor tissue (frozen and FFPE) with the non-small-cell lung carcinoma (NSCLC).  
PD-L1 expression was found to be inadequate as a biomarker to predict clinical outcome of patients’ undergoing immunotherapy.
This study revealed that neutrophil defensin 1, 2 and 3 has potential as biomarkers to predict the efficacy of current immunotherapy of NSCLC. MALDI Imaging showed that defensins are highly expressed in tumor margins and patients that showed response to immunotherapy had higher defensin expression. Presence of defensin was also confirmed with IHC staining on the same slide used in MALDI Imaging.
CCL5-CCR5 interactions modulate metabolic events during tumor onset to promote tumorigenesis
Gao D, et al., BMC Cancer, (2017)
DOI: 10.1186/s12885-017-3817-0  
Cancer biology: metabolism of tumor onset targeting metabolites.
Bruker product: solariX MRMS with SCiLS Lab analytical software suite.
Sample: Tumors from mice derived from triple negative breast cancer cell line MDA-MB-231.  
Chemokine biochemistry, specifically interaction of CCR5-CCL5, implicated in onset of breast cancer.
MALDI Imaging was able to track metabolic biomarkers that signal increase ATP and CTP activity and found that increased glucose uptake is found to be associated with CCL5 activation. In turn, CCL5 activation is correlated to early rapid tumor growth.
Murine stroma adopts a human-like metabolic phenotype in the PDX model of colorectal cancer and liver metastases
Blomme A, et al., Oncogene, (2017)
DOI: 10.1038/s41388-017-0018-x  
Cancer biology: patient derived xenograft (PDX) in mice targeting lipids and metabolites.
Bruker product: solariX MRMS with SCiLS Lab analytical software suite.
Sample: Tumors from mice derived from patient xenograft of colorectal (CRC) and CRC liver metastasized adenocarcinomas.
The potential of PDX biology being replaced or affected by murine stroma could present a serious validation problem in PDX based cancer research.
MALDI Imaging revealed that mouse stroma cells took on human-like phenotypes and is reflected in the metabolic and lipid profile. Quality control of PDX can potentially be validated by MALDI Imaging.
Native glycan fragments detected by MALDI-FT-ICR mass spectrometry imaging impact gastric cancer biology and patient outcome
Kunzke T, et al., Oncotarget, (2017).
DOI: 10.18632/oncotarget.19137  
Prognostic: correlating molecular biomarkers to patient clinical outcomes targeting glycans.
Bruker product: solariX MRMS
Sample: Human tumors of gastric adenocarcinomas.  
HexNAc–HexA–HexNAc glycan localized to tumor stoma regions was found to correlate to poor clinical outcome, which demonstrates potential as prognostic biomarkers.
Sia-Hex glycan was found to localize and positively correlate with epidermal growth factor receptor (EGFR), while HexA–HexNAc is negatively correlated to HER2/neu, indicating the interactions between glyco-saminoglycan fragments with EGFR and HER/neu.
Untargeted Metabolite Mapping in 3D Cell Culture Models Using High Spectral Resolution FT-ICR Mass Spectrometry Imaging
Tucker LH, et al., Analytical Chemistry, (2019).
DOI: 10.1021/acs.analchem.9b00661  
Cancer biology: metabolism of tumor spheroids targeting metabolites.
Bruker product: solariX MRMS with SCiLS Lab analytical software suite.
Sample: 3D cell culture tumor spheroids of breast cancer MCF-7 cell line.  
Probing metabolism within the microenvironment of multicellular tumor spheroids, as revealed by ATP/ADP ratio shown by MALDI Imaging of ATP and ADP distribution. Biomarkers also show increased oxidative and hypoxic stress at the center of the spheroid.
This study capitalizes on MRMS high accuracy for direct ion assignment and sensitivity.
Typing of colon and lung adenocarcinoma by high throughput imaging mass spectrometry
Kriegsmann M, et al., BBA - Proteins and Proteomics, (2017).
DOI: 10.1016/j.bbapap.2016.11.018  
Tissue typing: pathology of primary colon and lung cancer targeting proteins.
Bruker product: autoflex Speed MALDI-TOF/TOF with SCiLS Lab analytical software suite.
Sample: Human tumor of colon and lung adenocarcinomas.  
Analysis of metastatic tumor tissue in late cancer stages by traditional histopathology can be difficult.
Direct detection by MALDI Imaging of trypsin digested proteins on tissue allow statistical analysis to classify primary tumors from colon and lung, allowing objective and robust tumor typing.

 

For Research Use Only. Not for use in clinical diagnostic procedures.