Bone marrow as a metastatic niche for disseminated tumor cells from solid tumors

Shiozawa, Yusuke; Eber, Matthew R.; Berry, Janice E.; Taichman, Russell S.

doi:10.1038/bonekey.2015.57

Cited by 89 publications

(72 citation statements)

References 73 publications

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“…Unexpectedly, the transcriptional landscape of diagnostic DTCs resembled that of relapse DTCs to a large extent, although these patients had experienced multimodal treatment. This observation may be explained by the protective BM niche, just as it has been shown that the BM microenvironment promotes their survival, dormancy, growth and drug resistance . Remarkably, we found that the genes which were differentially expressed between diagnostic and relapse DTCs show a positional enrichment on chromosome 19, with five tumor suppressor genes being downregulated in relapse DTCs.…”

Section: Discussionmentioning

confidence: 63%

Neuroblastoma cells undergo transcriptomic alterations upon dissemination into the bone marrow and subsequent tumor progression

Rifatbegovic¹,

Frech²,

Abbasi³

et al. 2017

Intl Journal of Cancer

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Neuroblastoma is the most common extracranial solid tumor in childhood. The vast majority of metastatic (M) stage patients present with disseminated tumor cells (DTCs) in the bone marrow (BM) at diagnosis and relapse. Although these cells represent a major obstacle in the treatment of neuroblastoma patients, insights into their expression profile remained elusive. The present RNA‐Seq study of stage 4/M primary tumors, enriched BM‐derived diagnostic and relapse DTCs, as well as the corresponding BM‐derived mononuclear cells (MNCs) from 53 patients revealed 322 differentially expressed genes in DTCs as compared to the tumors (q < 0.001, |log2FC|>2). Particularly, the levels of transcripts encoded by mitochondrial DNA were elevated in DTCs, whereas, for example, genes involved in angiogenesis were downregulated. Furthermore, 224 genes were highly expressed in DTCs and only slightly, if at all, in MNCs (q < 8 × 10−75 log2FC > 6). Interestingly, we found the transcriptome of relapse DTCs largely resembling those of diagnostic DTCs with only 113 differentially expressed genes under relaxed cut‐offs (q < 0.01, |log2FC|>0.5). Notably, relapse DTCs showed a positional enrichment of 31 downregulated genes on chromosome 19, including five tumor suppressor genes: SIRT6, BBC3/PUMA, STK11, CADM4 and GLTSCR2. This first RNA‐Seq analysis of neuroblastoma DTCs revealed their unique expression profile in comparison to the tumors and MNCs, and less pronounced differences between diagnostic and relapse DTCs. The latter preferentially affected downregulation of genes encoded by chromosome 19. As these alterations might be associated with treatment failure and disease relapse, further functional studies on DTCs should be considered.

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Section: Discussionmentioning

confidence: 63%

Neuroblastoma cells undergo transcriptomic alterations upon dissemination into the bone marrow and subsequent tumor progression

Rifatbegovic¹,

Frech²,

Abbasi³

et al. 2017

Intl Journal of Cancer

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“…Bone metastases most commonly originate from breast and prostate tumors, and are generally associated with poor prognoses (Shiozawa et al, 2015). Osteotropic metastases can be characterized as osteolytic (stimulates bone destruction) or osteoblastic (stimulates bone formation), both of which are detrimental to the patient.…”

Section: Bone Metastases: Undercover Agents To Destroy and Invade Bonementioning

confidence: 99%

Unique Metabolic Adaptations Dictate Distal Organ-Specific Metastatic Colonization

et al. 2018

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Summary Metastases arising from tumors have the proclivity to colonize specific organs, suggesting that they must rewire their biology to meet the demands of the organ colonized, thus altering their primary properties. Each metastatic site presents distinct metabolic challenges to a colonizing cancer cell, ranging from fuel and oxygen availability to oxidative stress. Here, we discuss the organ-specific metabolic adaptations cancer cells must undergo, which provide the ability to overcome the unique barriers to colonization in foreign tissues and establish the metastatic tissue tropism phenotype.

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“…Once within the circulatory system, the neoplastic cells may invade the bone marrow and actively act in this microenvironment resulting in the development of metastatic neoplasia. The tumor growth is stimulated both by the activation of osteoclasts and by the release of growth factors within the bone marrow, and is inhibited by osseous formation and decreased osteoclastogenesis 13 , 18. It seems that the tumor gastric cells induce the differentiation and activation of the osteoclasts by the production of cytokines and via the RANK/RANKL system 19.…”

Section: Discussionmentioning

confidence: 99%

Bicytopenia and leukoerythroblastosis: a rare initial presentation of signet ring cell gastric adenocarcinoma

et al. 2017

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Gastric adenocarcinoma is a common neoplasia and is responsible for up to 30% of the overall deaths due to cancer. Advanced disease is mostly characterized by peritoneum, liver, and lung involvement. The spread of the disease to the bone is rare, and bone marrow dissemination is even rarer. In this setting, leukoerythroblastosis may be the initial manifestation of the disease. The authors report the case of a 64-year-old Caucasian man who sought medical care complaining of back pain, weakness, and weight loss. The physical examination revealed pallor, and the laboratory work-up depicted severe anemia and thrombocytopenia; the peripheral blood smear was consistent with leukoerythroblastosis. The ongoing investigation through a bone marrow biopsy showed massive involvement of the bone marrow by a signet ring cell adenocarcinoma. During hospitalization, the patient presented melena, and an upper digestive endoscopy depicted an ulcerated and infiltrative lesion in the cardia, upon which the histological examination revealed a signet ring cell adenocarcinoma. This case highlights the bone marrow invasion represented by bicytopenia and leukoerythroblastosis as the initial manifestation of this histological type of gastric cancer. Although treatment attempts were made with chemotherapy and radiotherapy, the patient died early on, showing the aggressive behavior of this form of tumoral presentation.

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Bone marrow as a metastatic niche for disseminated tumor cells from solid tumors

Cited by 89 publications

References 73 publications

Neuroblastoma cells undergo transcriptomic alterations upon dissemination into the bone marrow and subsequent tumor progression

Neuroblastoma cells undergo transcriptomic alterations upon dissemination into the bone marrow and subsequent tumor progression

Unique Metabolic Adaptations Dictate Distal Organ-Specific Metastatic Colonization

Bicytopenia and leukoerythroblastosis: a rare initial presentation of signet ring cell gastric adenocarcinoma

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