# The Role of Rarely Studied Chemokines in Tumor Progression in Multiple Myeloma (MM)

**Authors:** Jan Korbecki, Mateusz Bosiacki, Rafał Stelmach, Katarzyna Barczak

PMC · DOI: 10.3390/cancers18040673 · 2026-02-18

## TL;DR

This paper reviews the role of under-researched chemokines in multiple myeloma tumor progression and their effects on bone destruction and immune cell recruitment.

## Contribution

The paper highlights the underexplored roles of specific chemokines in multiple myeloma and their potential as therapeutic targets.

## Key findings

- Lesser-known chemokines like CXCL13 and CCL2 influence bone destruction and angiogenesis in MM.
- These chemokines affect immune cell recruitment and chemoresistance in the MM tumor niche.
- Bioinformatic analysis suggests these chemokines could be viable targets for MM therapy.

## Abstract

This review compiles current knowledge on the significance of lesser-known chemokines in multiple myeloma (MM) tumor processes, including CXCL13, CCR2 ligands (CCL2 [MCP-1], CCL7 [MCP-3]), CCL4, CCL5 (RANTES), CCL17, CCL20, CCL27, CCL28, and CX3CL1 (fractalkine). It describes their impact on bone destruction, bone marrow angiogenesis, chemoresistance, and the recruitment of cells into the MM niche, such as macrophages, myeloid-derived suppressor cells, and cytotoxic lymphocytes, along with their effects on mesenchymal stromal cells.

Multiple myeloma (MM) is a plasma cell neoplasm. Studies of chemokines in MM pathogenesis have primarily focused on CCR1 ligands such as CCL3 (MIP-1α), CXCL12 and its receptor CXCR4, as well as CXCR2 and CXCR3 ligands. However, the roles of the remaining 30 chemokines have been investigated much less frequently. This review compiles current knowledge on the significance of lesser-known chemokines in MM tumor processes, including CXCL13, CCR2 ligands (CCL2 [MCP-1], CCL7 [MCP-3]), CCL4, CCL5 (RANTES), CCL17, CCL20, CCL27, CCL28, and CX3CL1 (fractalkine). It describes their impact on bone destruction, bone marrow angiogenesis, chemoresistance, and the recruitment of cells into the MM niche, such as macrophages, myeloid-derived suppressor cells, and cytotoxic lymphocytes, along with their effects on mesenchymal stromal cells. A bioinformatic analysis highlights the significance of these chemokines in MM, and the possibility of targeting them in MM therapy is also considered.

## Linked entities

- **Genes:** CXCL13 (C-X-C motif chemokine ligand 13) [NCBI Gene 10563], CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347], CCL7 (C-C motif chemokine ligand 7) [NCBI Gene 6354], CCL4 (C-C motif chemokine ligand 4) [NCBI Gene 6351], CCL5 (C-C motif chemokine ligand 5) [NCBI Gene 6352], CCL17 (C-C motif chemokine ligand 17) [NCBI Gene 6361], CCL20 (C-C motif chemokine ligand 20) [NCBI Gene 6364], CCL27 (C-C motif chemokine ligand 27) [NCBI Gene 10850], CCL28 (C-C motif chemokine ligand 28) [NCBI Gene 56477], CX3CL1 (C-X3-C motif chemokine ligand 1) [NCBI Gene 6376]
- **Diseases:** multiple myeloma (MONDO:0009693), MM (MONDO:0009685)

## Full-text entities

- **Genes:** CCND3 (cyclin D3) [NCBI Gene 896], CCL14 (C-C motif chemokine ligand 14) [NCBI Gene 6358] {aka CC-1, CC-3, CKB1, HCC-1, HCC-1(1-74), HCC-1/HCC-3}, CCL8 (C-C motif chemokine ligand 8) [NCBI Gene 6355] {aka HC14, MCP-2, MCP2, SCYA10, SCYA8}, CCR7 (C-C motif chemokine receptor 7) [NCBI Gene 1236] {aka BLR2, CC-CKR-7, CCR-7, CD197, CDw197, CMKBR7}, JUN (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3725] {aka AP-1, AP1, c-Jun, cJUN, p39}, CCL19 (C-C motif chemokine ligand 19) [NCBI Gene 6363] {aka CKb11, ELC, MIP-3b, MIP3B, SCYA19}, CCL13 (C-C motif chemokine ligand 13) [NCBI Gene 6357] {aka CKb10, MCP-4, NCC-1, NCC1, SCYA13, SCYL1}, TNFRSF17 (TNF receptor superfamily member 17) [NCBI Gene 608] {aka BCM, BCMA, CD269, TNFRSF13A}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, CXCL14 (C-X-C motif chemokine ligand 14) [NCBI Gene 9547] {aka BMAC, BRAK, KEC, KS1, MIP-2g, MIP2G}, CCL25 (C-C motif chemokine ligand 25) [NCBI Gene 6370] {aka Ck beta-15, Ckb15, SCYA25, TECK, TECKvar}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CD2 (CD2 molecule) [NCBI Gene 914] {aka LFA-2, SRBC, T11}, CCL1 (C-C motif chemokine ligand 1) [NCBI Gene 6346] {aka I-309, P500, SCYA1, SISe, TCA3}, CXCL13 (C-X-C motif chemokine ligand 13) [NCBI Gene 10563] {aka ANGIE, ANGIE2, BCA-1, BCA1, BLC, BLR1L}, GPER1 (G protein-coupled estrogen receptor 1) [NCBI Gene 2852] {aka CEPR, CMKRL2, DRY12, FEG-1, GPCR-Br, GPER}, CXCR2 (C-X-C motif chemokine receptor 2) [NCBI Gene 3579] {aka CD182, CDw128b, CMKAR2, IL8R2, IL8RA, IL8RB}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, Cxcl13 (C-X-C motif chemokine ligand 13) [NCBI Gene 55985] {aka 4631412M08Rik, ANGIE2, Angie, BCA-1, BLC, BLR1L}, EPOR (erythropoietin receptor) [NCBI Gene 2057] {aka EPO-R}, CCR8 (C-C motif chemokine receptor 8) [NCBI Gene 1237] {aka CC-CKR-8, CCR-8, CDw198, CKRL1, CMKBR8, CMKBRL2}, CXCL16 (C-X-C motif chemokine ligand 16) [NCBI Gene 58191] {aka CXCLG16, SR-PSOX, SRPSOX}, PITPNM3 (PITPNM family member 3) [NCBI Gene 83394] {aka ACKR6, CORD5, NIR1, RDGBA3}, B2M (beta-2-microglobulin) [NCBI Gene 567] {aka AMYLD6, IMD43, MHC1D4}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, CXCR3 (C-X-C motif chemokine receptor 3) [NCBI Gene 2833] {aka CD182, CD183, CKR-L2, CMKAR3, GPR9, IP10-R}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, CCL24 (C-C motif chemokine ligand 24) [NCBI Gene 6369] {aka Ckb-6, MPIF-2, MPIF2, SCYA24}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, XCL2 (X-C motif chemokine ligand 2) [NCBI Gene 6846] {aka SCM-1b, SCM1B, SCYC2}, CCL15 (C-C motif chemokine ligand 15) [NCBI Gene 6359] {aka HCC-2, HMRP-2B, LKN-1, LKN1, MIP-1 delta, MIP-1D}, CXADRP1 (CXADR pseudogene 1) [NCBI Gene 653108] {aka CAR, CXADRP}, CCL16 (C-C motif chemokine ligand 16) [NCBI Gene 6360] {aka CKb12, HCC-4, ILINCK, LCC-1, LEC, LMC}, PGP (phosphoglycolate phosphatase) [NCBI Gene 283871] {aka AUM, G3PP, PGPase}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, CXCL9 (C-X-C motif chemokine ligand 9) [NCBI Gene 4283] {aka CMK, Humig, MIG, SCYB9, crg-10}, CCL3 (C-C motif chemokine ligand 3) [NCBI Gene 6348] {aka G0S19-1, LD78, LD78ALPHA, MIP-1-alpha, MIP1A, SCI}, CCL27 (C-C motif chemokine ligand 27) [NCBI Gene 10850] {aka ALP, CTACK, CTAK, ESKINE, ILC, PESKY}, LRP1 (LDL receptor related protein 1) [NCBI Gene 4035] {aka A2MR, APOER, APR, CD91, DDH3, IGFBP-3R}, CCL20 (C-C motif chemokine ligand 20) [NCBI Gene 6364] {aka CKb4, Exodus, LARC, MIP-3-alpha, MIP-3a, MIP3A}, SDC1 (syndecan 1) [NCBI Gene 6382] {aka CD138, SDC, SYND1, syndecan}, CCL5 (C-C motif chemokine ligand 5) [NCBI Gene 6352] {aka D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228}, MAF (MAF bZIP transcription factor) [NCBI Gene 4094] {aka AYGRP, CCA4, CTRCT21, c-MAF}, CD1C (CD1c molecule) [NCBI Gene 911] {aka BDCA1, CD1, R7}, FGFR3 (fibroblast growth factor receptor 3) [NCBI Gene 2261] {aka ACH, CD333, CEK2, HSFGFR3EX, JTK4}, CCL11 (C-C motif chemokine ligand 11) [NCBI Gene 6356] {aka SCYA11}, CCL26 (C-C motif chemokine ligand 26) [NCBI Gene 10344] {aka IMAC, MIP-4a, MIP-4alpha, SCYA26, TSC-1}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, MAFB (MAF bZIP transcription factor B) [NCBI Gene 9935] {aka DURS3, KRML, MCTO}, CCR5 (C-C motif chemokine receptor 5) [NCBI Gene 1234] {aka CC-CKR-5, CCCKR5, CCR-5, CD195, CKR-5, CKR5}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CCL21 (C-C motif chemokine ligand 21) [NCBI Gene 6366] {aka 6Ckine, CKb9, ECL, SCYA21, SLC, TCA4}, CCL28 (C-C motif chemokine ligand 28) [NCBI Gene 56477] {aka CCK1, MEC, SCYA28}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, CCR2 (C-C motif chemokine receptor 2) [NCBI Gene 729230] {aka CC-CKR-2, CCR-2, CCR2A, CCR2B, CD192, CKR2}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, IGF1R (insulin like growth factor 1 receptor) [NCBI Gene 3480] {aka CD221, IGFIR, IGFR, JTK13}, GPR35 (G protein-coupled receptor 35) [NCBI Gene 2859]
- **Diseases:** inflammatory (MESH:D007249), injury to (MESH:D014947), disease (MESH:D004194), CLL (MESH:D015451), Tumor (MESH:D009369), neurotoxicity (MESH:D020258), MM bone disease (MESH:D009101), renal failure (MESH:D051437), ATL (MESH:D015459), CML (MESH:D015464), skin rashes (MESH:D005076), sMM (MESH:D000075122), AML (MESH:D015470), osteolytic lesions (MESH:D030981), plasma cell malignancy (MESH:D054219), anemia (MESH:D000740), leukemia (MESH:D007938), immunodeficiency (MESH:D007153), neutropenia (MESH:D009503), extramedullary disease (MESH:D023981), cytotoxicity (MESH:D064420), osteolysis (MESH:D010014), bone destruction (MESH:D001847), hypercalcemia (MESH:D006934), renal dysfunction (MESH:D007674), organ damage (MESH:D000092124), PR (MESH:D008151), thymic atrophy (MESH:D013953), cytokine release syndrome (MESH:D000080424), allergic reactions (MESH:D004342), peripheral neuropathy (MESH:D010523), bone marrow tumor (MESH:D019046), mechanical allodynia (MESH:D006930), ISS (MESH:D062706), MS (MESH:D009103), solid (MESH:D018250), MGUS (MESH:D008998)
- **Chemicals:** pomalidomide (MESH:C467566), CCX140-B. (MESH:C585356), Bortezomib (MESH:D000069286), thalidomide (MESH:D013792), zymosan A (MESH:D015054), 5-HIAA (MESH:D006897), melphalan (MESH:D008558), elotuzumab (MESH:C546027), glycosaminoglycans (MESH:D006025), Lenalidomide (MESH:D000077269), dexamethasone (MESH:D003907), LPS (MESH:D008070), serotonin (MESH:D012701)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** rs2280788, rs2280789, rs2107538

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12940079/full.md

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Source: https://tomesphere.com/paper/PMC12940079