CD44
CD44 is a biomarker which is not only expressed in solid but also in hematological cancers (see below). Its expression is associated with increased proliferation, self-renewal and metastasis (61, 149, 462, 463). For example, in colorectal cancers, expression of CD44/CD166 characterizes a cell population able to form tumor spheres, suggesting anchorage-independent proliferation of these cells (333). In other studies, CD44high/CD133high cells showed increased tumorigenic capabilities (334). Also in breast cancers, the percentage of CD44+/CD24−/CK+/CD45− cells was shown to be increased in malignant lesions compared to non-malignant lesions (139). A significant decrease in proliferation and migration of breast cancer cells was observed after the knock-down of CD44 (140). In gastric cancers, the knock-down of CD44 reduced sphere formation and caused decreased tumor growth in severe combined immunodeficiency mice (246). In many tumors (e.g., breast and liver), CD44 is expressed as isoform and its expression has been associated with increased cancer stem cell properties (141). In lung cancers, CD44v9 expression correlates significantly with early-stage lung adenocarcinoma and epidermal growth factor receptor (EGFR) mutations (464). Variants of CD44 are also expressed in gastric cancers and promote tumor initiation (248).
The CSC marker CD44 has been indicated as a biomarker for diagnostic, therapeutic, and prognostic approaches (compare Tables 1–5). In gastric cancer patients, CD44+ circulating tumor cells correlated with a poor prognosis (465). In colorectal cancers, a prognostic quantitative real-time PCR was established to analyze the expression of CD44v2 showing that a high expression correlated with a worse prognosis (339). In gastric cancers, the expression of CD44 and CD90 correlated with distant metastasis and could therefore be used as a diagnostic biomarker (251) and was suggested as a biomarker for treatment response (253). Therapeutic approaches targeting CD44 have been made using e.g. adenoviral delivery of siRNA in vitro (337). Furthermore, CD44-targeting drug conjugated aptamers (76) or hyaluronic acid coated onto nanoparticles have been in the focus of research (155). Antibody-based photosensitizer conjugates for combined fluorescent detection and photo-immunotherapy (PIT) of CD44-expressing cells in triple-negative breast cancers (TNBC) (150) or other antibody-based approaches tested in safety studies (466–468).