Novel imaging technology and tools for biomarker detection in cancer

Abstract: Cancer is a leading cause of death worldwide. Normally the balance betweencell growth and cell death is strongly controlled. Chronic lymphocytic leukemiais an indolent disease that has a highly variable clinical course and is the mostcommon hematological malignancy amongst adults in the Western countries.The protein tyrosine phosphatase SHP-1 is a key regulator that controls theintracellular phosphotyrosine level in lymphocytes by inhibiting the B cell receptorsignals. We have compared the expression and activity of SHP-1 inchronic lymphocytic leukemia cells from lymph nodes with matched peripheralblood samples. The expression levels of SHP-1 were higher in peripheral blood,but the phosphatase activity in lymph nodes and peripheral blood did not differsignificantly. All cells in the body normally present glycans on the cell surface,which are involved in cellular communication and in processes like cell differentiation,proliferation and infection, including protecting the cells from invadersand in cell-cell contacts. Sialic acid occurs on the terminal end of glycans,and the frequency of sialic acid expression is increased on metastatic cancer cellsand overexpression controls tumor cell growth and cell differentiation. Theavailability of specific antibodies against sialic acid is limited. We have beenscreening sialic acid on cancer cells by using a molecular imprinting polymertechnique. Our results show that sialic acid is expressed on chronic lymphocyticleukemia cell lines at different levels at the plasma membrane. Higher expressionof sialic acid in the more aggressive chronic lymphocytic leukemia cell lineswas observed. To analyze morphological changes of death cells, digital holographicmicroscopy was used. Digital holographic microscopy is an approachfor label-free non-invasive 3D imaging of cultured cells. We have analyzed celldeath of adherent cancer cells using digital holographic microscopy and developedit to analyze suspension cells by combining this technique with antibodybased microassays. Digital holographic microscopy can be used for cell-deathinduced cell analysis of both adherent cells and suspension cells. This thesistakes us one step further in cancer research as regards developing techniques forscreening circulating cancer cells in blood as well as for individualized treatmentof cancer patients.