The tumor microenvironment promotes cancer progression and cell migration

Abstract

The tumor microenvironment contributes to cancer progression, in part through interactions between tumor and normal stromal cells. This study analyzed morphological and molecular changes induced in co-cultured human fibroblasts (HFs) and the MG-63 osteosarcoma cell line. Co-cultured cell monolayers were morphologically analyzed using high resolution scanning electron microscopy (HR-SEM), and trans-well assays were performed to assess cell migration and invasion. Proteins involved in inflammatory responses, cancer cell invasion, and angiogenesis were assessed using western blotting. HR-SEM showed progressive spatial orientation loss by fibroblasts in contact with MG-63s, while MG-63s proliferated rapidly and invaded HF space. Trans-well assays showed enhanced MG-63 migration in the presence of HFs. IL-6 expression was increased in co-cultured HFs, possibly stimulated by TNF-α. HFs do not normally express YKL-40 but did so in co-culture. Band densitometric analyses showed that increasing YKL-40 expression was followed by VEGF overexpression, especially in MG-63s. Finally, our results confirmed fibroblasts as the main matrix metalloproteinase source in this tumor microenvironment. Our study sheds new light on how tumor-stroma interactions promote tumor development and progression, and may support identification of novel anti-cancer therapeutics.

Neuronal Calcium Sensor 1 is up‐regulated in response to stress to promote cell survival and motility in cancer cells

“…NFκB is a central regulator of the cellular stress response (Mercurio and Manning, 1999) and can be activated by a broad range of stimuli (Pahl, 1999). Cancer cells are embedded in a very complex microenvironment that consists of a variety of such environmental stressors, including TNF‐α (Cairns et al , 2011; Landskron et al , 2014; Salvatore et al , 2017). NFκB is an established regulator of several pro‐survival and pro‐migratory genes (Baud and Karin, 2009; Ben‐Neriah and Karin, 2011; Hoesel and Schmid, 2013; Karin et al , 2002; Taniguchi and Karin, 2018), and many types of cancer have been linked to constitutive NFκB activation (Baud and Karin, 2009; Karin et al , 2002; Pires et al , 2017; Piva et al , 2006).…”

Dissection of prostate tumour, stroma and immune transcriptional components reveals a key contribution of the microenvironment for disease progression

“…Selected targets in the prostate tumour microenvironment have been extensively studied through in vitro and in vivo experiments, such as migration assays [10] and xenograft mouse models [11] respectively. More recently, several studies that integrated fluorescence-activated cell sorting (FACS) or laser microdissection with RNA sequencing increased the gene and sample throughput while maintaining a degree of resolution of the tissue heterogeneity [8,12,13].…”

Pathological and therapeutic aspects of matrix metalloproteinases: Implications in osteosarcoma

“…MMPs have also been shown to be involved in the regulation of multiple stages of cancer progression including cell growth, differentiation, apoptosis, migration, invasion, angiogenesis and metastasis . Elevated MMPs levels have been shown to be associated with metastasis and poor prognosis in several types of cancer including OS . Thus, it is necessary to counteract the activity of MMPs to inhibit cancer metastasis.…”