MMP1 and MMP11 Expression in Peripheral Blood Mononuclear Cells upon Their Interaction with Breast Cancer Cells and Fibroblasts

Abstract

Tumor-infiltrating immune cells phenotype is associated with tumor progression. However, little is known about the phenotype of the peripheral blood mononuclear cells (PBMC) from breast cancer patients. We investigated MMP1 and MMP11 expression in PBMC from breast cancer patients and we analyzed gene expression changes upon their interaction with cancer cells and cancer-associated fibroblasts (CAF). We measured the impact of PBMC on proinflammatory gene expression in breast cancer cells, normal fibroblast (NF), and CAF and the impact on proliferation and invasiveness capacity of breast cancer cells. Gene expression of MMP1 and MMP11 in PBMC from breast cancer patients (n = 54) and control (n = 28); expression of IL1A, IL6, IL17, IFNβ, and NFĸB in breast cancer cell lines (MCF-7 and MDA-MB-231); and, additionally, IL10 and MMP11 in CAF and NF were analyzed by qRT-PCR before and after co-culture. Our results show the existence of a subpopulation of breast cancer patients (25.9%) with very high levels of MMP11 gene expression in PBMC. Also, gene expression of MMP1 and MMP11 increases in PBMC after co-culture with breast cancer cell lines, NF or CAF. PBMC from healthy or breast cancer patients induce an increased proliferation rate on MCF-7 and an increased invasiveness capacity of MDA-MB-231. Finally, we show a differential expression profile of inflammatory genes in NF and CAF when co-cultured with control or breast cancer PBMC. We have observed that MMPs’ expression in PBMC is regulated by the microenvironment, while the expression of inflammatory genes in NF or CAF is differentially regulated by PBMC. These findings confirm the importance of the crosstalk between stromal cells and suggest that PBMC would play a role in promoting aggressive tumor behavior.

Identification of Significant Secreted or Membrane-Located Proteins in Laryngeal Squamous Cell Carcinoma

“…Our results showed that MMP1 and FSTL3 were significantly upregulated in LSCC and positively correlated with worse survival as well as several immune cells' infiltrations. MMP1 greatly promotes tumor cells' migration and invasion and has been reported to correlate with immune cells' infiltrations in breast and cervical cancer [ 26 , 27 ]. Eiro et al [ 28 ] found that MMP1 mediated the interaction among peripheral blood mononuclear cells, cancer cells, and cancer-associated fibroblasts.…”

Predicting 3D Structure, Cross Talks, and Prognostic Significance of KLF9 in Cervical Cancer

“…The plasma levels of several miRNAs, such as miR-218, miR-223, miR-7, miR30, and miR-21, were studied in hepatocellular carcinoma and gastric and ovarian cancer (62)(63)(64). Recently, the relative expressions of matrix metalloproteinases (MMPs) in blood of breast cancer patients were investigated to determine their role in cancer progression (65), hence indicating their possible application in disease prognosis. The current study also evaluated the mRNA expression of these molecules in blood of cervical cancer patients and provided a foundation for conducting an in-depth, proteomelevel analysis in vitro and in vivo.…”

Effect of Kaempferol on the Biological Behavior of Human Colon Cancer via Regulating MMP1, MMP2, and MMP9

“…Natural compounds draw increasing interest because of their anticancer effects at the molecular level. Kaempferol is a kind of flavonoid, which widely exists in a variety of natural foods and drugs [ 22 ]. MMPs is a family of calcium, zinc, and other metal ion-dependent endopeptidases, of which MMP1, 2, and 9 are three important members [ 23 ].…”