Globular C1q Receptor (gC1qR/p32/HABP1) Suppresses the Tumor-Inhibiting Role of C1q and Promotes Tumor Proliferation in 1q21-Amplified Multiple Myeloma.

Jiadai Xu,Peng Liu,Jifeng Jiang,Yifeng Sun,Jing Li,Zhao Xu,Tianhong Xu

doi:10.3389/fimmu.2020.01292

Abstract

Immunodeficiencies are widely becoming known as important features of multiple myeloma (MM) and may promote the proliferation of malignant cells as well as confer resistance to therapy. Few studies focus on the immunomodulatory effects of the complement system on MM. This study aims to explore the role of C1q in MM patients. Plasma C1q was found to be significantly reduced in MM patients, and the amount of C1q deposited around the CD138+ cells in bone marrow (BM) biopsy sections was observed to be much higher, especially in the subgroup with 1q21 amplification (Amp1q21). CD138+ cells expressed higher levels of C1q receptors (C1qRs) than CD138− cells. Patients with Amp1q21 expressed higher levels of globular C1qR (gC1qR), whereas patients without Amp21 expressed higher levels of collagen tail C1qR (cC1qR). Additionally, gC1qR was noted to suppress the MM-inhibiting role of C1q in H929, U266, and MM1S. gC1qR interacts with insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), which also suppressed the function of C1q and regulated CDC28 protein kinase regulatory subunit 1B (CKS1B) mRNA. In summary, gC1qR suppressed the MM-inhibiting role of C1q and regulated CKS1B mRNA in promoting tumor proliferation via IGF2BP3 in 1q21-amplified MM. Our findings provide novel evidence on how MM cells evade the immune system and promote survival as well as suggest possible novel targets for future therapies of MM.

Highlights

Multiple myeloma (MM), a hematological malignancy, is characterized by clonal plasma cells or plasma blasts that proliferate abnormally and evade death
This study provides novel evidence that globular C1qR (gC1qR) can suppress the tumor-inhibiting role of C1q and regulate CDC28 protein kinase regulatory subunit 1B (CKS1B) mRNA through IGF2BP3 in MM patients with Amp1q21
Far, research has clearly demonstrated that immune evasion, angiogenesis, and metastasis are potentially important in tumor survival and progression

Summary

Introduction

Multiple myeloma (MM), a hematological malignancy, is characterized by clonal plasma cells or plasma blasts that proliferate abnormally and evade death. Specific cytogenetic abnormalities, including del17p, t(14,16), t(4,14), and 1q21 amplification (Amp1q21) (1–3), indicate the poor prognosis of MM patients. Amp1q21, which is defined as having a copy number gain (copy numbers > 2) at chromosome 1 at band q21, is a frequently encountered karyotype abnormality in MM, which is an adverse phenotype closely related to the survival of MM patients. Despite emerging novel therapeutic strategies, response to treatment and final clinical outcomes are quite heterogeneous in MM patients. At present, this disease is considered to be mostly incurable

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