## 6 Farber disease
#### 3.5.2 GSLs in Cancer  
Cancer often displays distinctive GSL antigens that can function as adhesion molecules. These antigens interact with carbohydrate-binding proteins or corresponding carbohydrates on target cells, leading to diverse signaling events. This capability has the potential to initiate the metastatic process within cancer. Recent investigations have pinpointed specific GSL antigens that exhibit high expression in particular human cancer types. These antigens act as adhesion molecules, potentially fostering the spread of tumor cells. GSLs, particularly gangliosides and their degradation products, are believed to regulate cell growth by modulating essential molecules involved in signal transduction. Furthermore, GSLs play pivotal roles in upholding plasma membrane stability, governing various cellular processes such as adhesion, proliferation, apoptosis, and recognition. It is essential to recognize that various cells and tissues showcase differing GSL expression patterns. Structural modifications in GSL glycan components have also been observed during the progression of numerous human cancer forms [42, 192, 193, 194, 195, 196, 197]. Deviant expression of distinct GSLs and associated enzymes strongly correlates with tumor inception and the transformation into malignancy across numerous human cancer types [198, 199, 200, 201, 202, 203, 204]. However, the precise connections between the expression of diverse GSL species and the development of distinct cancer varieties remain incompletely understood. Furthermore, the molecular mechanisms through which GSLs influence cancer formation and advancement necessitate further clarification. Recent years have witnessed notable strides in utilizing GSLs as focal points for cancer immunotherapy and diagnostic approaches, considering the intricate and multifaceted contributions of GSLs to cancer evolution [85; 205; 206; 207]. The continuous evolution in glycobiology, including advancements in MS technology and the emergence of novel concepts and techniques, presents a promising avenue for deepening our comprehension of how GSLs influence the advancement of cancer. These strides create prospects for pioneering clinical utilities, delving into the untapped realm of cancer therapies built upon the abnormal expression of GSLs. Additional investigation is essential to comprehensively unravel the intricate connections between GSL expression and the progression of cancer. Likewise, there is a need to elucidate the underlying molecular mechanisms, which in turn will lay the groundwork for the development of more potent strategies for combating cancer. 1. Colon tumors  
Holst et al. [135] performed a study to determine glycosylation profiles of colorectal tumors in comparison to normal colorectal tissue, using MALDI-TOF (/TOF) MS. In order to increase the power of the study, paired samples were used containing normal and cancerous tissues from the same patient. Briefly, normal and cancerous tissue samples of 13 patients were used for isolating glycolipids (methanol/chloroform/water extraction); afterwards the GSLs from the upper phase were purified by reversed-phase solid-phase extraction (using C18-RP cartridges) and GSL-glycan release was performed using rEGCase II. The glycans were labeled using AA (2-aminobenzic acid) for facilitating detection in negative mode of neutral and negatively charged glycans, and after further purification by HILIC-SPE (hydrophilic interaction liquid chromatography solid-phase extraction), were applied to a stainless steel MALDI plate with DHB as a matrix. After statistical data processing, the authors discovered several significant changes. A general decrease in _globo_-series GSLs (Hex5 HexNAc2 NeuAc2 DHex1-AA at \(m/z\) 2082.70, as \(\left[\mathrm{M}\ -\ \mathrm{H}\right]^{-}\)) and acetylation (Ac1 Hex5 HexNAc2 NeuAc2 dHex1-AA at \(m/z\) 2036.72, as \(\left[\mathrm{M}\ -\ \mathrm{H}\right]^{-}\)). Interestingly, the _globo_-series GSLs were obtained by treating the GSLs with rEGCase II.