Metastatic breast cancer cells overexpress and secrete miR-218 to regulate type I collagen deposition by osteoblasts

Collagen is the major component of the tumor microenvironment and participates in cancer fibrosis. Collagen biosynthesis can be regulated by cancer cells through mutated genes, transcription factors, signaling pathways and receptors; furthermore, collagen can influence tumor cell behavior through integrins, discoidin domain receptors, tyrosine kinase receptors, and some signaling pathways. Exosomes and microRNAs are closely associated with collagen in cancer. Hypoxia, which is common in collagen-rich conditions, intensifies cancer progression, and other substances in the extracellular matrix, such as fibronectin, hyaluronic acid, laminin, and matrix metalloproteinases, interact with collagen to influence cancer cell activity. Macrophages, lymphocytes, and fibroblasts play a role with collagen in cancer immunity and progression. Microscopic changes in collagen content within cancer cells and matrix cells and in other molecules ultimately contribute to the mutual feedback loop that influences prognosis, recurrence, and resistance in cancer. Nanoparticles, nanoplatforms, and nanoenzymes exhibit the expected gratifying properties. The pathophysiological functions of collagen in diverse cancers illustrate the dual roles of collagen and provide promising therapeutic options that can be readily translated from bench to bedside. The emerging understanding of the structural properties and functions of collagen in cancer will guide the development of new strategies for anticancer therapy.

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“…Recent studies have highlighted the relationship among exosomes, microRNAs (miRNAs) and collagen in cancer [80][81][82].…”

Section: The Relationship Among Exosomes Micrornas and Collagen In Cmentioning

confidence: 99%

The role of collagen in cancer: from bench to bedside

et al. 2019

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“…There is increased collagen production at the bone metastatic site, whereby secreted collagen molecules are dense, misaligned, and disorganized, further disrupting bone mechanical function (Figure 5b) [66,75]. Liu et al identified that metastatic breast cancer cells secreted miR-218 which directly regulated type I collagen secretion from osteoblasts in the bone niche [76]. The authors further identified elevated levels of miR-218 in blood samples from patients with breast cancer bone metastases, suggesting miR-218 as a possible therapeutic for patients with bone metastatic breast cancer [76].…”

Section: The Bone Extracellular Matrixmentioning

confidence: 99%

The Bone Extracellular Matrix as an Ideal Milieu for Cancer Cell Metastases

Kolb

Bussard

2019

Cancers

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Bone is a preferential site for cancer metastases, including multiple myeloma, prostate, and breast cancers.The composition of bone, especially the extracellular matrix (ECM), make it an attractive site for cancer cell colonization and survival. The bone ECM is composed of living cells embedded within a matrix composed of both organic and inorganic components. Among the organic components, type I collagen provides the tensile strength of bone. Inorganic components, including hydroxyapatite crystals, are an integral component of bone and provide bone with its rigidity. Under normal circumstances, two of the main cell types in bone, the osteoblasts and osteoclasts, help to maintain bone homeostasis and remodeling through cellular communication and response to biophysical signals from the ECM. However, under pathological conditions, including osteoporosis and cancer, bone remodeling is dysregulated. Once in the bone matrix, disseminated tumor cells utilize normal products of bone remodeling, such as collagen type I, to fuel cancer cell proliferation and lesion outgrowth. Models to study the complex interactions between the bone matrix and metastatic cancer cells are limited. Advances in understanding the interactions between the bone ECM and bone metastatic cancer cells are necessary in order to both regulate and prevent metastatic cancer cell growth in bone.

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“…For instance, the let-7 family members (let-7a, let-7b, and let-7g) have been demonstrated to be poorly-expressed in the patients diagnosed with breast cancer with lymph node metastasis [9]. Previous work further illustrated the targeting relationship between miRNA and collagen in breast cancer [10]. Interestingly, through bioinformatics and a dual luciferase reporter gene assay, COL3A1 was suggested as a direct target of let-7b in neuronal injury [11].…”

Section: Introductionmentioning

confidence: 99%

Over-expression of CDX2 alleviates breast cancer by up-regulating microRNA let-7b and inhibiting COL11A1 expression

et al. 2020

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Background: microRNA Let-7 serves as a tumor suppressor by targeting various oncogenic pathways in cancer cells. However, the underlying mechanism of its involvement in breast cancer remains largely unknown. With our research, our endeavor is to explore the role of the CDX2/let-7b/COL11A1 axis in breast cancer cell activities. Methods: Tumor tissues and adjacent normal tissues were collected from 86 patients with breast cancer. Human breast cancer epithelial cell line MCF-7 was treated with over-expressed CDX2, let-7b mimic, shRNA against COL11A1 and their negative controls. The expression of CDX2, let-7b, and COL11A1 in the tissues and cells was determined by RT-qPCR. Interactions among CDX2, let-7b, and COL11A1 were detected by ChIP and dual-luciferase reporter assay, respectively. After different transfections, cell invasion, migration, and proliferation abilities were determined by Transwell and EdU assays. Lastly, tumor xenografts in nude mice were established and hematoxylin and eosin staining was performed to assess the tumor growth and lymph node metastasis. Results: CDX2 and let-7b were poorly expressed in breast cancer cells and tissues. CDX2 bound to let-7b and promoted the expression of let-7b, which contrarily inhibited the expression of COL11A1. Cancer cell proliferation, invasion, migration, and metastasis were stimulated when CDX2 and let-7b were depleted or COL11A1 was overexpressed. Xenograft tumors growth and metastasis were in accordance with the results of cellular experiments. Conclusion: In agreement with these observations, we could reach a conclusion that CDX2 could promote let-7b expression, which may exert an inhibitory effect on the proliferation, migration, and metastasis of breast cancer cells via repressing the expression of COL11A1, providing a novel therapeutic strategy for the treatment of metastatic breast cancer.

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Metastatic breast cancer cells overexpress and secrete miR-218 to regulate type I collagen deposition by osteoblasts

Cited by 62 publications

References 40 publications

The role of collagen in cancer: from bench to bedside

The role of collagen in cancer: from bench to bedside

The Bone Extracellular Matrix as an Ideal Milieu for Cancer Cell Metastases

Over-expression of CDX2 alleviates breast cancer by up-regulating microRNA let-7b and inhibiting COL11A1 expression

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