Spatial mass spectrometry is increasingly being used to answer a question bulk measurements cannot: where is a molecular change happening, and what does that location reveal about disease?
For metabolites, glycans, and extracellular matrix peptides, that context can be crucial. These targets influence transport, signaling, tissue structure, and disease progression, but their biological meaning often depends on where they appear in relation to cells, gradients, and microenvironments. A recent MS imaging webinar by US HUPO highlighted this point through two examples: glucose uptake in cataract biology and N-glycan and extracellular matrix peptide mapping in pancreatic cancer.
Mapping Glucose in the Lens
Gus Gray, Associate Professor in the Department of Physiology at the University of Auckland, described work using spatial metabolomics and proteomics to study ocular lens transparency and cataract formation.
The lens has no blood supply, but it must maintain a precise structure to transmit light. Cells at the edge of the lens are young, while cells in the core are as old as the individual. These gradients in cell age, protein composition, water content, and refractive index make the lens a useful but challenging system for spatial analysis.
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Gray’s group used isotopically labeled glucose and FT-ICR MALDI imaging to track glucose uptake and metabolism in bovine lens tissue. Early uptake appeared in the germinative and equatorial regions, where lens cells grow and migrate. Over time, labeled glucose spread through much of the tissue. Glucose-6-phosphate followed a related but delayed pattern, while sorbitol showed a different distribution, with early accumulation on the anterior surface.
These findings are significant because glucose metabolism supports the lens microcirculation system that drives ion transport, water movement, and nutrient delivery. In diabetes, excess glucose can contribute to cataract formation. One route involves conversion of glucose to sorbitol, which draws water into lens cells and disrupts the ordered tissue structure.
Gray’s team also used proteomics to examine glucose transporters. In bovine lens tissue, GLUT1 appeared most abundant in peripheral epithelial and fiber cells, matching regions of labeled glucose uptake. In human lenses, the team identified GLUT12, a transporter that showed different localization patterns depending on lens region. That finding raises questions about glucose regulation in the human lens and its possible role in diabetic cataract.
Glycans and Pancreatic Cancer
Caroline Kittrell, an MD-PhD candidate in the laboratory of Richard Drake at the Medical University of South Carolina, presented work using MALDI mass spectrometry imaging to study pancreatic ductal adenocarcinoma.
Her team is mapping N-glycans and extracellular matrix peptides in formalin-fixed paraffin-embedded tissue. The work includes primary pancreatic tumors, liver and lung metastases, and a large tissue microarray spanning normal adjacent tissue, pancreatitis, premalignant lesions, and pancreatic cancer.
In primary tumors, the team detected bisecting N-glycans with core and outer-arm fucosylation that localized with cancer regions. Multiplex immunohistochemistry helped show that some of these glycans aligned with CK19-positive tumor cells. For extracellular matrix peptides, MALDI MSI peaks were matched with LC-MS/MS proteomics data, linking many signals to fibrillar collagens in the tumor microenvironment.
The metastatic tissue results added another layer. The N-glycome of pancreatic cancer, liver metastases, and lung metastases clustered together and away from normal adjacent tissues, suggesting a tumor-associated glycan signature. The extracellular matrix profiles told a different story: metastatic samples appeared more similar to their native liver or lung environments than to primary pancreatic tumors. Kittrell suggested this may reflect pancreatic cancer co-opting the ECM machinery of metastatic sites.
Early tissue microarray findings also pointed to disease-stage differences. Some collagen peptides increased in pancreatic cancer, pancreatitis, and premalignant tissue, suggesting ECM remodeling may begin before invasive cancer appears.
From Molecular Lists to Spatial Maps
Both talks showed how spatial MS can connect molecular distributions with disease mechanisms. In the lens, imaging tracked glucose metabolism across tissue regions and linked uptake patterns to transporter biology. In pancreatic cancer, imaging revealed glycan and ECM signatures across primary, metastatic, and premalignant tissue states.
For analytical scientists, the work also highlights persistent method challenges. Small molecules such as glucose can be difficult to ionize and interpret. Peptide and glycan assignments need orthogonal validation. Tissue alignment, region selection, and multimodal data integration remain central to confident interpretation.
The wider takeaway is that spatial mass spectrometry can move sugar-related analysis beyond detection. By preserving location, researchers can see how metabolites, glycans, and matrix components shape disease environments—and where those patterns may support future therapeutic or biomarker strategies.
