ABSTRACT
; Aim To culture primary human gastric cancer associated fibroblasts (CAFs) and normal fibroblasts (NFs), and to explore the biological characteristics and their effects on gastric cancer cells. Methods After isolation and culture of CAFs and NFs, growth curve was drawn by MTT. The a-smooth muscle actin (ot-SMA) and Vimentin were detected by Immunofluorescence, Western blot and qRT-PCR. MGC-803 cells were co-cultured with CAFs and NFs in Transwell suspension mode. The migration and invasion ability of gastric cancer cells was detected by Transwell. The proliferation activity and AMD3100 on CAFs-gastric cancer co-culture system were compared by MTT. The acidic property, lactic acid and ROS contents of co-culture system were determined by PH meter, lactic acid and DCFH-DA method. Results The morphology of CAFs, NFs cells were in long spindle or flat star shape. The proliferation ability and overlapping growth phenomenon of CAFs were higher than those of NFs. The expression of ct-SMA and Vimentin cells was positive in CAFs, but low or negative in NFs cells. The activity of gastric cancer in low density co-culture group > medium density group > high density group, the PH value of CAFs co-culture system decreased, the content of lactic acid and ROS was high, and only CAFs low density co-culture group had significant effect on promoting cancer. Conclusions The co-culture of gastric cancer cells with CAFs and NFs is greatly affected by the proportion. Low density co-culture can significantly improve the proliferation and metastasis ability of gastric cancer cells. High density co-culture may in turn inhibit the growth and metastasis of cancer cells, which may be related to the content of lactic acid and ROS.
ABSTRACT
The growth of tumour cells is closely related to cancer-associated fibroblasts (CAFs)present within their microenvironment. CAFs, the most abundant cells in tumour stroma, secretegrowth factors that play pivotal roles in tumour cell proliferation, metabolism, angiogenesis andmetastasis. Tumour cells adapt to rapid environmental changes from normoxia to hypoxia throughmetabolic interplay with CAFs. In this mini review, we discuss the role of lactate dehydrogenases(LDHs) and monocarboxylate transporters (MCTs) on the metabolic interplay between tumourcells and CAFs under hypoxia compared to normoxia. The LDHs catalyse the interchange oflactate and pyruvate, whereas MCTs facilitate the influx and efflux of monocarboxylates, especiallylactate and pyruvate. To sum up, tumour cells switch their metabolic state between glycolysis andoxidative phosphorylation through metabolic interplay with CAFs, which exhibit the Warburgeffect under hypoxia and reverse Warburg effect under normoxia.
ABSTRACT
Cancers acquire reprogramming of energy metabolism to balance energy production and their biosynthetic needs. The altered metabolism includes aerobic glycolysis, glutaminolysis, reverse Warburg effect and truncated tricarboxylic acid cycle. Cancer cells principally rely on aerobic glycolysis through mitochondrial dysfunction, changes of key metabolic players, hypoxic microenvironment, and genomic changes. Understanding the style and mechanisms of cancer energy metabolism may lead to development of new approaches to reverse metabolic reprogramming.