CD44 in Cancer

Abstract

CD44 is a multistructural and multifunctional cell surface molecule involved in cell proliferation, cell differentiation, cell migration, angiogenesis, presentation of cytokines, chemokines, and growth factors to the corresponding receptors, and docking of proteases at the cell membrane, as well as in signaling for cell survival. All these biological properties are essential to the physiological activities of normal cells, but they are also associated with the pathologic activities of cancer cells. Experiments in animals have shown that targeting of CD44 by antibodies, antisense,and CD44-soluble proteins markedly reduces the malignant activities of various neoplasms, stressing the therapeutic potential of anti-CD44 agents. Furthermore, because alternative splicing and posttranslational modifications generate many different CD44 sequences, including, perhaps, tumor-specific sequences, the production of anti-CD44 tumor-specific agents may be a realistic therapeutic approach. However, in many cancers (renal cancer and non-Hodgkin's lymphomas are exceptions), a high level of CD44 expression is not always associated with an unfavorable outcome. On the contrary, in some neoplams CD44 upregulation is associated with a favorable outcome. Even worse, in many cases different research grows analyzing the same neoplastic disease reached contradictory conclusions regarding the correlation between CD44 expression and disease prognosis, possibly due to differences in methodology. These problems must be resolved before applying anti-CD44 therapy to human cancers.

Anticancer Therapeutics: Targeting Macromolecules and Nanocarriers to Hyaluronan or CD44, a Hyaluronan Receptor

“…This goal has been achieved to some extent with anti-CD44 antibody-drug conjugates, which target drugs to CD44 that is overexpressed on various tumors. 13 Anti-CD44 antibody-drug conjugates have shown promise during clinical development (Table 2). However, CD44 is endogenously expressed at low levels in healthy tissues; 17 because of this expression, side effects still occur.…”

“…10 -12 Changes in both CD44 and HA expression have been widely observed in tumors from cancer patients and occur in animal models of tumor growth. 13 During carcinogenesis, expression of the standard form of CD44 is upregulated in certain cancers. Non-native CD44 variants may also arise from alternate splicing of cytoplasmic regions of CD44 during translation.…”

“…Non-native CD44 variants may also arise from alternate splicing of cytoplasmic regions of CD44 during translation. 13 Interference with the CD44-HA interaction by either targeting drugs to CD44, 14 targeting drugs to the HA matrix 15 or interfering with HA matrix-CD44 interactions 16 are viable strategies for cancer treatments. The CD44-HA system is illustrated in Figure 2.…”

Targeted therapy aimed at cancer stem cells: Wilms’ tumor as an example

“…Several of these antigens have been known to be expressed in different malignancies, long before their implication as CSC markers. However, their specific targeting was put forward as means to treat human malignancies only following the revelation of their role in signifying the CSC population [67,81,82].…”

Hepatocyte Growth Factor-induced Ras Activation Requires ERM Proteins Linked to Both CD44v6 and F-Actin

“…Expression of a v6 containing CD44 isoform conferred the metastatic potential to otherwise nonmetastatic cells (Gü nthert et al, 1991). Furthermore, CD44 variants have been detected in a variety of human tumors and their expression has been correlated with poor prognosis (for review, see Naor et al, 2002).…”