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Tumor Discovery Bioinformatics insights into CCL2 mutations

A

B

Figure 8. Mutation of cysteine (C59) to glycine (G59) in the CCL2 protein led to substantial structural changes. (A) Native CCL2 structure, where the bond
distances between C59 and the neighboring amino acids K58 and P60 were 9.6 and 6.5 Å, respectively. (B) CCL2 mutant G59 structure, where these bond
distances increased to 11.7 Å between G59 and K58 and 7.1 Å between G59 and P60. These changes in bond distances indicate that the mutation disrupted
the local interactions and altered the overall folding of the protein.
Abbreviation: CCL2: Chemokine C-C motif ligand 2.

this axis helps overcome therapy resistance. In lung and influencing tumor progression. Further investigation
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cancer, CCL2 recruits myeloid-derived suppressor cells in cohorts of patients with cancer is needed to validate this
(MDSCs) and tumor-associated macrophages, reducing mutation’s clinical relevance and potential as a therapeutic
the effectiveness of immune checkpoint inhibitors, target.
whereas its inhibition increases chemotherapy sensitivity. CCL2 plays a critical role in macrophage recruitment
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In renal cell carcinoma, the elevated expression of CCL2 is and activation. Mutations that affect CCL2’s ability to bind
linked to poor survival, promoting angiogenesis, and the to its receptor CCR2 could alter macrophage behavior,
accumulation of MDSCs. CCL2 also enhances bladder impacting inflammatory responses and tumor-associated
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cancer cell migration and infiltration, indicating that its macrophage dynamics. For example, mutations that
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blockade may improve responses to both chemotherapy impair CCL2 function might reduce macrophage
and immunotherapy. In colorectal cancer, CCL2 is infiltration into tumors, potentially affecting tumor
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involved in metastasis and angiogenesis, highlighting growth and metastasis. Monocytes migrate into tissues
5
its potential as a prognostic marker and therapeutic by activating integrins on their surface through the
target. Overall, targeting the CCL2–CCR2 axis presents CCL2–CCR2 axis. This activation facilitates the processes
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a promising strategy for cancer treatment across multiple of rolling and adhesion, which allow monocytes to pass
tumor types. Our findings on the C59G mutation offer through the vascular endothelium and enter the tissues.
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insights into its potential role in modulating CCL2 activity The CCL2–CCR2 axis activates monocytes, macrophages,

Volume 3 Issue 4 (2024) 18 doi: 10.36922/td.3891