Investigating the Molecular Specific Interactions on Cell Surface Using Atomic Force Microscopy

Abstract

Cancer is the leading cause of death in economically developed countries and the second leading cause of death in developing countries [1]. The new cancer cases will increase from 12.7 million in 2008 to 22.2 million by 2030, while the cancer-related deaths will increase from 7.6 million in 2008 to 13.2 million by 2030 [2]. Carcinogenesis and tumor progression are complex and progressive processes that are associated with numerous genetic and epigenetic alterations [3]. Our growing understanding of tumor biology and genomics paves the way to the development of new therapy approaches, and marked progress has been achieved in overcoming treatment resistance through precision medicine and immunotherapy [4]. However, because of the fact that the exact reason why a cell becomes cancerous is unknown (the only one cancer whose cause is clear is cervical cancer), the current cancer treatments cannot prevent the recurrence of cancers and the age-adjusted mortality rate for cancer is about the same in the twenty-first century as it was 50 years ago [5].Lymphomas, solid tumors of the immune system [6], account for 4%-5% of all cancers [7]. Hodgkin's lymphoma accounts for about 10% of all lymphomas and the remaining 90% are referred to as non-Hodgkin lymphoma (NHL) [6]. NHL can be divided into many subtypes according to the combination of morphology, immunophenotype, genetic, molecular, and clinical features of the tumors [8]. Approximately, 85% of NHL in adults arises from B cells [9], and the rest are T-cell origin [10]. Follicular lymphoma and diffuse large B-cell lymphoma are the two most common B-cell NHLs, comprising 60% of new B-cell NHL diagnoses each year in North America [11]. In 1997, US Food and Drug Administration (FDA) approved rituximab (an anti-CD20 monoclonal antibody (mAb)) for treating B-cell NHLs. CD20 is 297 amino acids long with a molecule weight of about 33 kDa [12]. The exact biological function of CD20 is currently unknown [13], partly because it has no known natural ligand and CD20 knockout mice display an almost normal phenotype [14]. Many of the functions of CD20 have been determined using artificial ligands (antibody) [15]. In vitro experiments proposed that CD20