Biomedical Engineering Reference
In-Depth Information
expression of JAM-C on non-small lung cancer cells has been shown to promote
tumor cell adhesion to JAM-C-expressing endothelial, suggesting that homophilic
JAM-C interactions may be involved in tumor metastasis. h is has been remarkably
coni rmed in two independent studies using the HT1080 human i brosarcoma cell
line. In one study, Fuse and collaborators showed a strong positive correlation
between JAM-C expression and the metastatic potential of cancer cell lines (Fuse
et al.
2007). In another study, JAM-C was identii ed by a proteomic approach as
one of 47 molecules dif erentially expressed between two HT1080 variant cell lines
dif ering in their ability to intravasate and disseminate (Conn
et al.
2008). h ese
i ndings strongly suggest a role for JAM-C in tumor mestastasis. In contrast to
JAM-C, the level of JAM-A expression has been inversely correlated to the ability
of breast cancer cells to intravasate (Naik
et al.
2008). Finally, one single study
on leukemic patients has shown that JAM-C is highly expressed in hairy cell
leukemias and in marginal zone B-cell lymphomas but not on chronic lymphocytic
leukemias, suggesting that JAM-C could be used as diagnosis marker in leukemias.
h us, dif erential expression of the JAMs is expected in molecular signatures of
metastatic versus non-metastatic cancers and might be used as a prognosis marker
in certain tumors. However, these preliminary observations await coni rmation
through a meta-analysis of gene and protein expression patterns in larger panels
of the dif erent tumors.
CONCLUSIONS
h e ability of JAMs to undergo numerous homo- and heterophilic interactions
highlights their role in mediating interactions between immune cells and endothelial
or epithelial cells and suggests a critical role for JAMs during inl ammations. Small
molecule inhibitors or antibodies blocking homophilic JAM interactions and as
a consequence heterotypic cell interactions might thus turn out to be useful in
inhibiting unwanted immune reactions such as chronic inl ammations. On the
other hand, the identii cation of evolutionarily conserved cytoplasmic binding
partners of JAMs, some of which are involved in the fundamental process of cellular
polarization, indicates that JAMs participate in the regulation of cell polarity. h eir
wide expression in various cell types suggests a similar role in dif erent cell types and
organ systems. h e involvement of JAM-C in spermatid development as well as in
nerve conduction by mediating heterotypic and autotypic interactions, respectively,
strongly supports this notion. Furthermore, there is good evidence for a role for
JAM-A in endothelial and epithelial cell migration as well as in proliferation. h e
correlation of JAM-C expression with the tumorigenic potential of various cell
lines suggests that misregulation of JAM-C expression might contribute to tumor
and metastasis formation. As during inl ammatory reactions, inhibitors blocking
JAM interactions could turn out to be useful in inhibiting tumor growth. In future,
