Hepatic complications of breast cancer

Diamond, Jennifer R.; Finlayson, Christina; Borges, Virginia F.

doi:10.1016/s1470-2045(09)70029-4

Cited by 69 publications

(54 citation statements)

References 44 publications

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“…1,2 In the later stages of progression, BC cells metastasize from the original tumor site and travel through the vasculature to distant organs such as liver, lungs, brain, and bone. [2][3][4][5] Although the involvement of cell adhesion molecules in cancer development, progression, and metastasis has been established and discussed extensively in the literature, the mechanisms underlying their implication is still nascent. 6 -9 The hyaluronan (HA) receptor CD44, a multistructural and multifunctional cell adhesion molecule involved in cell-cell and cell-extracellular matrix interactions, functions as a bioactive signaling transmitter involved in a variety of cellular responses, including lymphocyte homing, hematopoiesis, inflammation, tumorigenesis, angiogenesis, and metastasis.…”

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confidence: 99%

Survivin Is a Novel Target of CD44-Promoted Breast Tumor Invasion

Abdraboh

Gaur

Hollenbach

et al. 2011

The American Journal of Pathology

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The hyaluronan (HA) receptor CD44 plays an essential role in cell-cell or cell-extracellular matrix communications and is a bioactive signal transmitter. Although a number of studies have described the function of CD44 in breast cancer (BC) metastasis, the underlying mechanisms have yet to be determined. By using a validated tetracycline-off-regulated CD44 expression system in the MCF-7 cell line combined with microarray analysis, we identified survivin (SVV) as a potential downstream transcriptional target of CD44. To test the hypothesis that SVV underpins CD44-promoted BC cell invasion, we combined molecular and pharmacologic approaches and showed that CD44 induction increased SVV expression levels, which in turn promotes BC cell invasion. Further, clinical analysis of breast tissue samples showed that SVV expression patterns paralleled those of the standard form of CD44 during breast tumor progression. More interestingly, we identified the PI3K/E2F1 pathway as a potential molecular link between HA/CD44 activation and SVV transcription. In addition to identifying SVV as a target for HA/CD44 signaling, this investigation provides a better understanding of the molecular mechanisms that underpin the novel function of SVV in breast cancer metastasis. Breast cancer (BC) is the most common cancer and the second most common cause of cancer-related deaths in women in the United States, with more than 175,000 women being diagnosed annually. 1,2 In the later stages of progression, BC cells metastasize from the original tumor site and travel through the vasculature to distant organs such as liver, lungs, brain, and bone. [2][3][4][5] Although the involvement of cell adhesion molecules in cancer development, progression, and metastasis has been established and discussed extensively in the literature, the mechanisms underlying their implication is still nascent. 6 -9 The hyaluronan (HA) receptor CD44, a multistructural and multifunctional cell adhesion molecule involved in cell-cell and cell-extracellular matrix interactions, functions as a bioactive signaling transmitter involved in a variety of cellular responses, including lymphocyte homing, hematopoiesis, inflammation, tumorigenesis, angiogenesis, and metastasis. 10 -13 The CD44 -HA complex initiates a series of intracellular signaling events that lead to migration, adhesion, invasion, proliferation, and differentiation of a variety of cells. The transduction of HA/CD44 signaling can occur through various mechanisms including the following: i) HA binding to CD44 can initiate the extracellular clustering of CD44, resulting in the activation of downstream kinases, 14 ii) CD44 can serve as a co-receptor physically associated with other cell signaling receptors, [15][16][17][18] iii) CD44 can serve as a docking protein for pericellular or cytoplasmic proteins, 19,20 and iv) the transmembrane domain of CD44 can be cleaved, allowing the translocation of the cytoplasmic domain to the nucleus, where it functions as a transcription factor regulating the expression of target gen...

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confidence: 99%

Survivin Is a Novel Target of CD44-Promoted Breast Tumor Invasion

Abdraboh

Gaur

Hollenbach

et al. 2011

The American Journal of Pathology

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“…To address this issue, we utilized liver resection specimens and biopsy material from patients with breast cancer liver metastases. Few patients meet the criteria for partial hepatic resection for breast cancer liver metastases (Selzner et al, 2000;Er et al, 2008;Diamond et al, 2009); however, we were able to analyze 24 breast cancer liver metastases. Importantly, our data indicates that claudin-2 is expressed in all liver metastases from breast cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Claudin-2 is selectively enriched in and promotes the formation of breast cancer liver metastases through engagement of integrin complexes

et al. 2010

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The liver represents the third most frequent site of metastasis in patients with breast cancer. We performed in vivo selection using 4T1 breast cancer cells to identify genes associated with the liver metastatic phenotype. Coincident with the loss of numerous tight-junctional proteins, we observe claudin-2 overexpression, specifically in liver-aggressive breast cancer cells. We further demonstrate that claudin-2 is both necessary and sufficient for the ability of 4T1 breast cancer cells to colonize and grow in the liver. The liver-aggressive breast cancer cells display a claudin-2-mediated increase in their ability to adhere to extracellular matrix (ECM) components, such as fibronectin and type IV collagen. Claudin-2 facilitates these cell/matrix interactions by increasing the cell surface expression of a 2 b 1 -and a 5 b 1 -integrin complexes in breast cancer cells. Indeed, claudin-2-mediated adhesion to fibronectin and type IV collagen can be blocked with neutralizing antibodies that target a 5 b 1 and a 2 b 1 complexes, respectively. Immunohistochemical analyses reveal that claudin-2, although weakly expressed in primary human breast cancers, is readily detected in all liver metastasis samples examined to date. Together, these results uncover novel roles for claudin-2 in promoting breast cancer adhesion to the ECM and define its importance during breast cancer metastasis to the liver.

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“…The most frequently reported cause of pseudocirrhosis is metastatic breast cancer treated with chemotherapy [4][5][6][7][8][9][10][11][12][13][14] , which commonly presents with diffuse nodular changes of the liver surface on ct imaging 15 . However, the liver can also become nodular and resemble cirrhosis after hepatic metastasis in pancreatic, esophageal, and small-cell lung cancer [16][17][18] .…”

Section: Differential Diagnosismentioning

confidence: 99%

Medullary Thyroid Cancer and Pseudocirrhosis: Case Report and Literature Review

et al. 2012

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and spindle-cell morphologies, and a diagnosis of medullary thyroid carcinoma (mtc) was made.On baseline positron-emission tomography (pet)/ ct imaging, hypodensities corresponding to hypermetabolic foci in both hepatic lobes were observed [ Figure 1 , and cytokeratin 7, but negative for thyroglobulin, cytokeratin 20, and alpha-fetoprotein, which is consistent with mtc metastatic to the liver. At the time of diagnosis, the patient was not taking medications, and she had an unremarkable personal medical history and no family history of thyroid disease, endocrine disorders, or neoplasm.In March 2008, the patient enrolled in a phase i clinical trial (NCT00599924) of 5-fluorouracil (5fu), leucovorin, and oxaliplatin (folfox) in combination with sunitinib, a tyrosine kinase inhibitor with multiple targets, including the vascular endothelial growth factor receptor and the rearranged during transfection (RET) proto-oncogene, which is often upregulated in neuroendocrine tumors such as mtc 1 . The patient received folfox (leucovorin 400 mg/m 2 ; 5-fluorouracil 400 mg/m 2 intravenous bolus, followed by 2400 mg/m 2 infusion over 46 hours; oxaliplatin 85 mg/m 2 ) every 2 weeks and sunitinib 37.5 g daily for 4 weeks, followed by a 2-week rest period. In July 2008, after 4 months of folfox-sunitinib, the patient showed measureable tumor regression in the liver [Figure 1(D)] that qualified as a partial response according to the Response Evaluation Criteria in Solid Tumors. The folfox was discontinued, and the patient was maintained on single-agent sunitinib, which she tolerated well for 15 months with stable liver metastases. The patient underwent serial pet/ ct imaging without intravenous contrast to monitor her disease.In November 2009 (21 months after diagnosis), the patient developed abdominal bloating, early satiety, and right upper quadrant pain that increased with inspiration. Pulmonary exam demonstrated dullness ABSTRACT Pseudocirrhosis is a rare form of liver disease that can cause clinical symptoms and radiographic signs of cirrhosis; however, its histologic features suggest a distinct pathologic process. In the setting of cancer, hepatic metastases and systemic chemotherapy are suspected causes of pseudocirrhosis. Here, we present a patient with medullary thyroid carcinoma metastatic to the liver who developed pseudocirrhosis while on maintenance sunitinib after receiving 5-fluorouracil, leucovorin, and oxaliplatin (folfox) in combination with sunitinib. Cirrhotic change in liver morphology was accompanied by diffusely infiltrative carcinomatous disease resembling the primary tumor. We discuss the diagnosis of pseudocirrhosis in this case and review the literature regarding pseudocirrhosis in cancer. KEY WORDSMedullary thyroid cancer, pseudocirrhosis, carcinomatous cirrhosis CASE DESCRIPTIONA 49-year-old white woman presented in January 2008 with a left-sided cervical mass without associated complaints of neck pain, stridor, dysphonia, dysphagia, malaise, fever, or chills. Physical examination was remarkable for a f...

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Hepatic complications of breast cancer

Cited by 69 publications

References 44 publications

Survivin Is a Novel Target of CD44-Promoted Breast Tumor Invasion

Survivin Is a Novel Target of CD44-Promoted Breast Tumor Invasion

Claudin-2 is selectively enriched in and promotes the formation of breast cancer liver metastases through engagement of integrin complexes

Medullary Thyroid Cancer and Pseudocirrhosis: Case Report and Literature Review

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