A widely expressed free immunoglobulin ? chain with a unique V?4-1/J?3 pattern promotes colon cancer invasion and metastasis by activating the integrin?1/FAK pathway

Historically, immunoglobulin (Ig) has been known as an antibody and is expressed only in B lineage cells; importantly, Ig light chains are conjugated to heavy chains to form intact Igs. However, in this study, we found a free Ig kappa light chain with a unique V kappa 4-1/J kappa 3 rearrangement (V kappa 4-1/J kappa 3-FLC) that was widely expressed in different non-B lineages and was overexpressed in cancer cells. Further study indicated that V kappa 4-1/J kappa 3-FLC was hydrophobic, formed obvious insoluble deposits in the extracellular matrix (ECM) and existed in free form. Functional analyses demonstrated that V kappa 4-1/J kappa 3-FLC promoted the proliferation, migration and metastasis of colon cancer cells in vitro and in vivo. Mechanistically, V kappa 4-1/J kappa 3-FLC bound to integrin beta 1 and activated the FAK and Src pathways. More importantly, specific antibodies against the variable region of V kappa 4-1/J kappa 3-FLC significantly inhibited the growth of colon cancer tumors. Our findings suggested that V kappa 4-1/J kappa 3-FLC is a novel ECM protein and integrin beta 1 ligand and that it is involved in cancer progression and is a potential therapeutic target in cancer, particularly colon cancer.

Automated summary

In this study, a free Ig kappa light chain V kappa 4-1/J kappa 3-FLC, normally expressed in B lineage cells, was found to be widely expressed in non-B lineages and overexpressed in cancer cells, promoting cancer cell proliferation, migration, and metastasis by binding to integrin beta 1 and activating FAK and Src pathways. Specific antibodies against V kappa 4-1/J kappa 3-FLC variable region significantly inhibited colon cancer tumor growth.