The metabolism of cancer cells during metastasis

Abstract

Metastasis formation is the major cause of death in most patients with cancer. Despite extensive research, targeting metastatic seeding and colonization is still an unresolved challenge. Only recently, attention has been drawn to the fact that metastasizing cancer cells selectively and dynamically adapt their metabolism at every step during the metastatic cascade. Moreover, many metastases display different metabolic traits compared with the tumours from which they originate, enabling survival and growth in the new environment. Consequently, the stage-dependent metabolic traits may provide therapeutic windows for preventing or reducing metastasis, and targeting the new metabolic traits arising in established metastases may allow their eradication.The metastatic establishment of cancers at distant organs is largely uncurable and primarily contributes to the deaths of cancer patients. Nonetheless, metastasis for-mation itself is a rare event in tumours because cancer cells need to overcome multiple environmental hur-dles before they can successfully manifest themselves in other organs 1,2 . As a first step, cancer cells need to become motile, invasive and intravasate the tumour vasculature to enter the bloodstream, either directly or via the lymphatic system. Although numerous cancer cells can find their way into the circulation, the majority will succumb during their journey, with only few able to extravasate, expand and successfully colonize other organs 3 . Clinical observations and multiple experi-mental studies have led to several propositions that can explain the acquired metastatic traits of cancer cells (as described and summarized elsewhere 2-7

Osmium(ii) tethered half-sandwich complexes: pH-dependent aqueous speciation and transfer hydrogenation in cells

“…[59][60][61][62] In particular, lactate and pyruvate are key cell metabolites that the tumour cell requires to promote cancer invasion as they help circulating tumour cells to survive by enhancing their resistance against oxidative stress. 63 Osmium(II) arene [Os(η 6 -p-cymene)(impy-NMe 2 )Cl/I]PF 6 (impy = iminopyridine) can oxidize NADH to NAD + by Os-driven hydride abstraction. 64 Importantly, chiral 16-electron complex [Os(η 6 -p-cymene)(TsDPEN)], (TsDPEN = N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine), inspired by the Noyori-type of catalysts for asymmetric transfer hydrogenation (TH), 65 is capable of catalysing asymmetric reduction of pro-chiral pyruvate to lactate using non-toxic doses of sodium formate as a hydride donor inside cells.…”

“Metabolic dysregulations of cancer cells with metastatic potential”

“…Dysregulated metabolism plays a vital role in cancer cell progression and metastasis [22,23,25,26,45–49]. In this study, we have shown that TNBC cell lines differentiating in their metastatic potential in vivo exhibit different metabolic profile already in vitro, and those differences are independent of the abundance of canonical EMT markers.…”

ATP and cancer immunosurveillance

“…Adenosine triphosphate (ATP) occupies a key position in the overall configuration of the TME. On one hand, intracellular ATP is crucial for each cellular TME component to survive and mediate its functions (including proliferation, for malignant and non‐terminally differentiated immune cells) (Leone & Powell, 2020; Bergers & Fendt, 2021). On the other hand, the pool of ATP that accesses the TME upon active secretion by living or dying cells into the extracellular space constitutes a major signal transducer (Di Virgilio et al , 2018).…”