Current progress and mechanisms of bone metastasis in lung cancer: a narrative review

Abstract

Lung cancer is a kind of malignant tumor with rapid progression and poor prognosis. Distant metastasis has been the main cause of mortality among lung cancer patients. Bone is one of the most common sites. Among all lung cancer patients with bone metastasis, most of them are osteolytic metastasis. Some serious clinical consequences like bone pain, pathological fractures, spinal instability, spinal cord compression and hypercalcemia occur as well. Since the severity of bone metastasis in lung cancer, it is undoubtedly necessary to know how lung cancer spread to bone, how can we diagnose it and how can we treat it. Here, we reviewed the process, possible mechanisms, diagnosis methods and current treatment of bone metastasis in lung cancer. We divided the process of bone metastasis in lung cancer into three steps: tumor invasion, tumor cell migration and invasion in bone tissue. It may be influenced by genetic factors, microenvironment and other adhesion-related factors. Imaging examination, laboratory examination, and pathological examination are used to diagnose lung cancer metastasis to bone. Surgery, radiotherapy, targeted therapy, bisphosphonate, radiation therapy and chemotherapy are the common clinical treatment methods currently. We also found some problems remained to be solved. For example, drugs for skeletal related events mainly target on osteoclasts at present, which increase the ratio of patients in osteoporosis and fractures in the long term. In all, this review provides the direction for future research on bone metastasis in lung cancer.

MicroRNA-106a regulates autophagy-related cell death and EMT by targeting TP53INP1 in lung cancer with bone metastasis

“…Approximately 30–40% of lung cancer patients eventually develop bone metastasis (BM), but the treatment of these patients is extremely poor [ 2 ]. Moreover, BM brings persistent pain to the patient and increases the risk of fracture, seriously affecting the quality of life of the patient [ 3 , 4 ]. Therefore, fully understanding the signalling networks involved in BM of lung cancer is essential for the development of novel anti-metastatic strategies.…”

Upregulated osteoprotegerin expression promotes lung cancer cell invasion by increasing miR‑20a expression

“…Metastasis is a multifactorial and multistep dynamic process, which are the primary causes of poor prognosis and mortality associated with cancer ( 38 ). Patients with advanced lung cancer are more prone to bone metastasis, which seriously affects their daily activities and reduces their quality of life ( 39 ).…”

Lung adenocarcinoma cell-derived exosomal miR-328 promote osteoclastogenesis by targeting Nrp2

“…We seeded RAW264.7 cells on 48-well plates ((1× 10 4 )) in D-MEM (Gibco, USA) supplemented with 10% FBS (Gibco, USA). M-CSF (30ng/ml) and RANKL (100ng/ml) were used to promote osteoclast maturation for 7 days.…”

“…Bone metastasis is the second most frequent site of lung cancer metastasis 1 and most lung cancer bone metastasis can be classified into osteolytic bone metastasis 2 , which can cause pain, pathological, spinal instability, spinal cord compression and hypercalcemia and result in a decline in the quality of life 3,4 . However, lung cancer cells can not directly lead to osteolytic metastasis by proteolytic enzymes.…”