Analysis of gene expression involved in brain metastasis from breast cancer using cDNA microarray

Nishizuka, Itaru; Ishikawa, Takashi; Hamaguchi, Yohei; Kamiyama, Masako; Ichikawa, Yasushi; Kadota, Koji; Miki, Rika; Tomaru, Yuji; Mizuno, Yosuke; Tominaga, Naoko; Yano, Rieko; Gotō, Hitoshi; Nitanda, Hiroyuki; Togo, Shinji; Okazaki, Yasushi; Hayashizaki, Yoshihide; Shimada, Hiroshi

doi:10.1007/bf02967543

Cited by 44 publications

(29 citation statements)

References 13 publications

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“…It has also been observed that the release of cytokines by glial cells contributes to the growth and metastatic potential of tumor cells within brain tissue. 7 The MDA-MB-231 tumor line has been a wellestablished model for metastatic bone tumors after intracardiac injection, even though the development of tumors in other tissues has been observed. 12 It is notable that the manipulation of this line in an attempt to develop clones with more specificity to bone or brain required multiple passages through mice where tumors colonizing the bone or brain were harvested, expanded, and reinjected into new mice.…”

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confidence: 99%

Unexpected Preferential Brain Metastases with a Human Breast Tumor Cell Line MDA-MB-231 in BALB/c Nude Mice

et al. 2008

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Abstract. Animal models are useful tools to study etiology, progress, and new treatments of disease and are an approximation of human disease for experimental study. Intracardiac injection of the human estrogen-independent breast cancer cell line MDA-MB-231 in nude mice is a well-characterized animal model of bone metastasis mainly used to study new treatments for late-stage breast cancer. According to the published literature, this model should produce radiologically distinguishable bone tumors within 17 days after injection. Mice should develop complications such as cachexia, paraplegia, and morbidity within 28 days and require euthanasia within 35 days after injection. We report a study in which injection of MDA-MB-231 cell line led to brain rather than bone metastasis. Unexpected alterations in biological behavior are an important confounding variable in the use of tumor cell lines, and the occurrence and cause of such variants is poorly documented.

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confidence: 99%

Unexpected Preferential Brain Metastases with a Human Breast Tumor Cell Line MDA-MB-231 in BALB/c Nude Mice

et al. 2008

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“…Functional analysis indicated that metastatic colonization occurs as a result of the cancer cells' modification following interaction with the surrounding environment in the liver. Other investigators also reported similar results (16,33,34). Nishizuka et al (34) reported that cytokines produced by glial cells in vivo may contribute in a paracrine manner to the development of brain metastases from breast cancer cells.…”

Section: Discussionmentioning

confidence: 66%

“…Other investigators also reported similar results (16,33,34). Nishizuka et al (34) reported that cytokines produced by glial cells in vivo may contribute in a paracrine manner to the development of brain metastases from breast cancer cells. Metastatic colonization differs from growth in the primary lesion by its requirement for angiogenesis, and changes in the local microenvironment in metastatic lesions and stressful conditions.…”

Section: Discussionmentioning

confidence: 66%

The gene expression profile represents the molecular nature of liver metastasis in colorectal cancer

Yamasaki

Takemasa²,

Komori³

et al. 2007

Int J Oncol

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Abstract. The major cause of death in colorectal cancer is related to liver metastasis. Although the metastatic process has been well studied, many aspects of the molecular genetic basis of metastasis remain unclear. Elucidation of the molecular nature of liver metastasis is urgent to improve the outcome of colorectal cancer. We analyzed the chronological gene expression profiles of 104 colorectal samples corresponding to oncogenic development including normal mucosa, localized and metastasized primary tumors, and liver metastatic lesions as fundamental samples using a custom cDNA microarray. The gene expression patterns in 104 samples were classified into four groups closely associated with their metastatic status, and the genes of each group appropriately reflected the metastatic process. To investigate the existence of metastatic potential in primary tumors using metastasis-related genes detected by chronological analysis, we performed a hierarchical cluster and supervised classification analysis of 28 independent primary tumors. Hierarchical cluster analysis segregated the tumors according to their final metastatic status, rather than their clinical stages, and the profile of metastasized primary tumors resembled one of a metastatic lesion apart from a primary lesion rather than one of a non-metastasized primary tumor. Using the supervised classification approach, the expression profile of these genes allowed the classification of tumors diagnosed as localized cancer into two classes, the localized and the metastasized class, according to their final metastatic status. The disease-free survival and overall survival were significantly longer in the localized class than the metastasized class. Chronological analysis of the gene expression profile provides a better understanding of the metastatic process. Our results suggest that the metastatic potential is already encoded in the primary tumor and is detectable by a gene expression profile, which allows the prediction of liver metastasis in patients diagnosed with localized tumors and also the design of new strategies for the treatment and diagnosis of colorectal cancer.

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“…Over the last few years, several studies have been conducted using microarray to identify i) genes related to the metastases of primary breast tumors (11), ii) genes expressed differentially between normal individuals and cancer patients (12) and iii) changes in the gene expression pattern before and after chemotherapy (13). However, no genome-wide studies conducted to date have been limited to cytokineassociated genes or designed to clarify the complex network and relationships of cytokines with tumor and immune cells.…”

Section: Introductionmentioning

confidence: 99%

Analysis of the expression profiles of cytokines and cytokine-related genes during the progression of breast cancer growth in mice

Jung

Kim²,

Cho

et al. 2009

Oncol Rep

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Abstract. Cytokines are a protein family of regulatory factors derived from tumors and their environmental components that contribute to the growth, invasion and metastasis of breast cancer. However, the way in which tumor progression and cytokines regulate each other is not well understood. In this study, we used an oligoDNA microarray to assess the kinetic expression profile of cytokine genes in tumor tissues and lymph nodes during the progression of tumor growth in mice that had been subcutaneously challenged with breast adenocarcinoma SB5b cells. Our results demonstrated that IL-15, IL-17, IL-18 and IL-18 binding protein (IL-18bp), which are associated with inflammation, were increased in tumor tissues. Conversely, chemokines and their receptors, including CXCR4/CXCL12, CCR7/CCL21, CCL9, CXCL9 and CCL12, were overexpressed in lymph nodes during tumor growth. Furthermore, RT-PCR and Western blot analysis revealed that IL-18, a pro-angiogenic factor in tumors, was up-regulated in tumor tissues. Interestingly, CCR3, IL-1R2, SOCS and IL-20 were up-regulated in tumor tissues, but down-regulated in lymph nodes during tumor growth. This result suggests that the expression of cytokines and cytokine-related genes was differentially regulated, which resulted in a beneficial effect for tumor progression.

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Analysis of gene expression involved in brain metastasis from breast cancer using cDNA microarray

Abstract: These results suggest that cytokines produced by glial cells in vivo may contribute, in a paracrine manner, to the development of brain metastases from breast cancer cells.

Cited by 44 publications

References 13 publications

Unexpected Preferential Brain Metastases with a Human Breast Tumor Cell Line MDA-MB-231 in BALB/c Nude Mice

Unexpected Preferential Brain Metastases with a Human Breast Tumor Cell Line MDA-MB-231 in BALB/c Nude Mice

The gene expression profile represents the molecular nature of liver metastasis in colorectal cancer

Analysis of the expression profiles of cytokines and cytokine-related genes during the progression of breast cancer growth in mice

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