Lipidomics Research On Cancer Cell Lines With Different Metastatic Potential

Cancer is a major health issue and the leading cause of human death.Gastric cancer,breast cancer,lung cancer and colorectal cancer are within the most common malignancies worldwide,which have high rates of morbidity and mortality.Lung cancer and breast cancer rank first in males and females,respectively,for morbidity and mortality.Gastric caner and colorectal cancer are within the top five most frequently diagnosed cancer in males and females.Metastasis is the most important characteristic and leading cause to cancer death.However,the molecular mechanism of carcinogenesis,cancer progression and metastasis is still unclear.Therefore,understanding the molecular mechanism in cancer metastasis,screening of metastasis-related biomarker and targeted moleculars for metastasis intervention are the main emphasis and assignment in the field of cancer research.With the improvement of lipidomics theory and technology,evidences of substantial studies haved showed disruption of lipid metabolism is correlatedwith carcinogenesis,cancer progression and metastasis in various cancers.To clarify the transformations in lipid profiling associated with metastasis of gastric cancer,breast cancer,lung cancer and colorectal cancer,3 gastric cancer cell lines,3 breast cancer cell lines,2 lung cancer cell lines and 2 colorectal cancer cell lines with different metastatic potential but similar gene background were selected to construct cell models of gastric cancer metastasis,breast cancer metastasis,lung cancer metastasisand colorectal cancer metastasis,respectively.But,cells from different models have different gene background.Untargeted shotgun lipidomis method was applied to perform global lipid profiling of three lipid classes,including glycerophospholipid,sphingolipid and glyceride on the ten selected cell lines.Both precursor ion scans and neutral loss scans were performed in positive and negative ion modes.After normalization of the obtained data,univariate analyses and multivariate analyses were conducted to perform comparative lipidomics analysis.Finally,a total of 2217 lipid moleculars were identified in all the ten selected cell lines.On the comparative lipidomics analysis to cell lines with different anatomical origin,433 differential lipids were screened out,results of Hierarchical Clustering analysis showed cell lines with different anatomical origin could be separated into four obvious clusters.Relative quantitative analysis showed obviously decreased PE levels and absent expressed of C22:6(DHA)containing lipids in the two lung cancer cell lines A549 and NCI-H1299.On the comparative lipidomics analysis to cell lines with different metastaticpotential in each models,105 differential lipids in gastric cancer model,110 differential lipids in breast cancer model,144 differential lipids in lung cancer model and 73 differential lipids in colorectal cancer model were observed to be associated with cancer metastasis,respectively.Results of HCA,PCA and PLS-DA revealed cell lines with different metastatic potential were separated obviously in gastric cancer,lung cancer and colorectal cancer,except that there is partial overlap in breast cancer.The key changes associated with increased metastatic potential in abnormal sphingolipid metabolism include decreased CerP level in gastric cancer,increased HexCer levels in breast and lung cancer but decreased level in colorectal cancer and increased Cer level in lung cancer.The key changes associated with increased metastatic potential in abnormal glycerophospholipid metabolism include increased PE,PA,PI levels and decreased LPC level in gastric cancer,while most of the glycerophospholipid subclasses in colorectal cancer were decreased.The key changes associated with increased metastatic potential in abnormal fatty acid metabolism include decreased C16:0 and C18:1 level in breast and lung cancer,increased C16:1level in gastric cancer,decreased PUFAs levels in gastric and colorectal cancer but increased levels in breast and lung cancer.This study suggests that:1.There are vast differences in lipid composition between cells from different anatomical origins.This discovery is of vital importance for investigating disease pathogenesis in different tissues and organs.And the differential lipidmolecules identified should be used as potential histiocyte-specific biomarkers.2.Lipid profiling and lipid levels change obviously with increased metastatic potential of cancer cells from the same native tissue but with different metastatic potential.The cancer metastasis related differential lipids should be used as potential biomarkers for cancer metastasis,providing basis for further screening of clinical biomarkers.The changes of lipid metabolism could provide some suggestions for investigating cancer metastasis related lipid metabolic parthways and looking for cancer therapeutic targets.