Background Cancer stem cells (CSCs) play crucial role in tumor progression, drug resistance and relapse in various cancers. CSC niche is comprised of various stromal cell types including Tumor-associated macrophages (TAMs). Extrinsic ques derived from these cells help in maintenance of CSC phenotype. TAMs have versatile roles in tumor progression however their function in enrichment of CSC is poorly explored. Methods Mouse macrophages (RAW264.7) cells were activated by interaction with conditioned media (CM) of murine breast cancer cells (4T1) into TAMs and the effect of activated macrophage (TAM) derived factors was examined on enrichment of cancer stem cells (CSCs) and tumor growth using in vitro and in vivo models. Results In this study, we report that macrophages upon interaction with breast cancer cells activate tumor promoting function and exhibit differential expression of various proteins as shown by secretome analysis using proteomics studies. Based on secretome data, we found that Interleukin-6 (IL-6) is one of the up-regulated genes expressed in activated macrophages. Further, we confirm that TAMs produce high levels of IL-6 and breast cancer cell derived factors induce IL-6 production in activated macrophages via p38-MAPK pathway. Furthermore, we demonstrate that tumor activated macrophages induce enrichment of CSCs and expression of CSC specific transcription factors such as Sox-2, Oct-3/4 and Nanog in breast cancer cells. We further prove that TAM derived IL-6 plays a key role in TAM mediated CSC enrichment through activation of Signal transducer and activator of transcription 3 (STAT-3) signaling. TAM derived IL-6 influences breast cancer cell migration and angiogenesis. Moreover, our in vivo findings indicated that TAM derived IL-6 induces CSC population and resulting tumor growth in breast cancer. Conclusion These finding provide evidence that TAM derived IL-6 plays a major role in CSC enrichment and tumor progression in breast cancer and IL-6 and its regulated signalling network may act as potential therapeutic target for management of breast cancer.

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Multiple myeloma (MM) is a plasma cell-associated cancer and exists as the second most common hematological malignancy worldwide. Although researchers have been working on MM, a comprehensive quantitative Bone Marrow Interstitial Fluid (BMIF) and serum proteomic analysis from the same patients’ samples is not yet reported. The present study involves the investigation of alterations in the BMIF and serum proteome of MM patients compared to controls using multipronged quantitative proteomic approaches viz., 2D-DIGE, iTRAQ, and SWATH-MS. A total of 279 non-redundant statistically significant differentially abundant proteins were identified by the combination of three proteomic approaches in MM BMIF, while in the case of serum 116 such differentially abundant proteins were identified. The biological context of these dysregulated proteins was deciphered using various bioinformatic tools. Verification experiments were performed in a fresh independent cohort of samples using immunoblotting and mass spectrometry based SRM assays. Thorough data evaluation led to the identification of a panel of five proteins viz., haptoglobin, kininogen 1, transferrin, and apolipoprotein A1 along with albumin that was validated using ELISA in a larger cohort of serum samples. This panel of proteins could serve as a useful tool in the diagnosis and understanding of the pathophysiology of MM in the future.