A novel human recombinant single-chain antibody targeting CD166/ALCAM inhibits cancer cell invasion in vitro and in vivo tumour growth

Wiiger, Merete Thune; Gehrken, Hege B.; Fodstad, Øystein; Mælandsmo, Gunhild M.; Andersson, Yvonne

doi:10.1007/s00262-010-0892-3

Cited by 43 publications

(28 citation statements)

References 33 publications

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“…In melanoma, silencing ALCAM expression in high-ALCAM expressed cell line a showed reduction of cell motility and invasiveness (Jannie et al, 2012). Moreover, blocking ALCAM with single-chain antibody inhibited invasiveness of breast cancer (Wiiger et al, 2010). On the contrary, our results showed that blocking ALCAM with the antibody did not affect invasion of CCA even when increasing to very high concentrations.…”

Section: Discussioncontrasting

confidence: 54%

ALCAM is a Novel Cytoplasmic Membrane Protein in TNF-α Stimulated Invasive Cholangiocarcinoma Cells

Adisakwattana

Suwandittakul²,

Petmitr³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: Cholangiocarcinoma (CCA), or bile duct cancer, is incurable with a high mortality rate due to a lack of effective early diagnosis and treatment. Identifying cytoplasmic membrane proteins of invasive CCA that facilitate cancer progression would contribute toward the development of novel tumor markers and effective chemotherapy. Materials and Methods: An invasive CCA cell line (KKU-100) was stimulated using TNF-α and then biotinylated and purified for mass spectrometry analysis. Novel proteins expressed were selected and their mRNAs expression levels were determined by real-time RT-PCR. In addition, the expression of ALCAM was selected for further observation by Western blot analysis, immunofluorescent imaging, and antibody neutralization assay. Results: After comparing the proteomics profile of TNF-α induced invasive with non-treated control cells, over-expression of seven novel proteins was observed in the cytoplasmic membrane of TNF-α stimulated CCA cells. Among these, ALCAM is a novel candidate which showed significant higher mRNA-and protein levels. Immunofluorescent assay also supported that ALCAM was expressed on the cell membrane of the cancer, with increasing intensity associated with TNF-α. Conclusions: This study indicated that ALCAM may be a novel protein candidate expressed on cytoplasmic membranes of invasive CCA cells that could be used as a biomarker for development of diagnosis, prognosis, and drug or antibody-based targeted therapies in the future.

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Section: Discussioncontrasting

confidence: 54%

ALCAM is a Novel Cytoplasmic Membrane Protein in TNF-α Stimulated Invasive Cholangiocarcinoma Cells

Adisakwattana

Suwandittakul²,

Petmitr³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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“…Wiiger et al (16) described a human recombinant single-chain antibody targeting ALCAM that was able to inhibit cancer cell invasion in vitro and in vivo tumor growth. Furthermore, Roth et al (35) described an internalizing single chain antibody that targets ALCAM in prostate cancer cells and immunoliposomes using this antibody were developed in order to deliver liposomal drugs to prostate cancer cells (35).…”

Section: Alcam Ihc Results ------------------------------------------mentioning

confidence: 99%

“…An association between high ALCAM expression and unfavorable prognosis has been shown for colorectal (7), pancreatic (9) and esophageal squamous cell cancer (8), and neuroblastoma (12). As a membrane protein, ALCAM also represents a potential target for therapy, which has already been successfully targeted by human recombinant single-chain antibody in breast cancer cells (16).…”

Section: Introductionmentioning

confidence: 99%

Loss of ALCAM expression is linked to adverse phenotype and poor prognosis in breast cancer: A TMA-based immunohistochemical study on 2,197 breast cancer patients

et al. 2014

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Abstract. Activated leukocyte cell adhesion molecule (ALCAM) is a membranous cell adhesion protein that is often expressed in breast cancer. Data on the prognostic impact of ALCAM expression is highly controversial in this cancer. To evaluate the clinical impact of ALCAM expression in a sufficiently large patient cohort, we utilized a tissue microarray (TMA) containing more than 2,100 primary breast cancers with clinical follow-up data by immunohistochemistry. TMA spots containing normal breast epithelium showed moderate to strong membranous ALCAM staining. ALCAM staining was strong in 66.2%, moderate in 10.9%, weak in 11.1% and absent in 11.8% of 1,778 (80.9%) interpretable breast cancer tissue spots. Decreased ALCAM expression was significantly associated with advanced tumor size (p=0.0017), unfavorable tumor grade (p<0.0001), negative ER and PR status (p<0.0001 each) as well as high Ki67 labeling index (p<0.0001). Cancers with ACLAM expression loss had a significantly poorer overall (p<0.0001) and disease-specific survival (p= 0.0088). This association also held true in the subset of nodal positive cancers (p<0.0001). In conclusion, these data demonstrate that ALCAM is generally expressed in normal and cancerous breast epithelium and that a marked reduction of ALCAM expression characterizes a subset of breast cancer patients with adverse tumor characteristics and unfavorable clinical outcome.

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“…CD166 is involved in hematopoiesis (19,20), neurite extension (21), osteogenesis (22), and embryonic implantation in the uterus (23). The level of CD166 expression correlates with the aggregation and metastatic potential of a few human tumors (24), including melanoma (25,26) and prostate (27,28), ovarian (29), breast (30 -32), colorectal (33,34), esophageal (35), and pancreatic cancer (36,37). Furthermore, AL-CAM was also identified in medium conditioned by breast cancer cells and may be a potential serum breast cancer biomarker (38,39).…”

Section: Discussionmentioning

confidence: 99%

Plasma Membrane Proteomics of Tumor Spheres Identify CD166 as a Novel Marker for Cancer Stem-like Cells in Head and Neck Squamous Cell Carcinoma

Yan

Yang

Wang

et al. 2013

Molecular & Cellular Proteomics

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Patients with advanced head and neck squamous cell carcinoma (HNSCC) have a poor prognosis with the currently available therapy, and tumor recurrence is frequently observed. The discovery of specific membraneassociated cancer stem cell (CSC) markers is crucial for the development of novel therapeutic strategies to target these CSCs. To address this issue, we established sphere cultures to enrich CSCs and used them for plasma membrane proteomics to identify specific membrane signatures of the HNSCC spheres. Of a dataset that included a total of 376 identified proteins, 200 were bona fide membrane proteins. Among them, 123 proteins were at least 1.5-fold up-or down-regulated in the spheres relative to the adherent cultures. These proteins included cell adhesion molecules, receptors, and transporter proteins. Some of them play key roles in wnt, integrin, and TGF␤ signaling pathways. When we compared our dataset with two published hESC membrane protein signatures, we found 18 proteins common to all three of the databases. CD166 and CD44 were two such proteins. Interestingly, the expression of CD166, rather than that of the wellestablished HNSCC CSC marker CD44, was significantly related to the malignant behavior of HNSCC. Relative to Head and neck squamous cell carcinoma (HNSCC)1 is the sixth most common cancer worldwide. Despite ongoing improvement in traditional treatments, the long-term survival rate of patients with HNSCC has not significantly improved over the past several decades. More than 60% of patients with advanced tumors or localized lymph node metastases die within five years of their diagnosis (1). Tumor recurrence and resistance to therapy are the major causes of death. Recently, newly recognized cancer stem cells (CSCs) or tumor-initiating cells have been associated in a cause-andeffect manner with tumor recurrence and resistance to therapy. The concept of CSCs was established because of the heterogeneous nature of cancer and suggests that CSCs are a subpopulation of cancer cells with stem-cell-like traits and the source of all cells in the cancer. Conventional cancer therapies such as chemotherapy and radiotherapy may destroy only those cells that form the bulk of the tumor, leaving the CSCs intact and able to give rise to tumor recurrence. Based on this theory, researchers are searching for therapies that would destroy CSCs in the hope of finally curing cancer (2). In order to develop strategies that target CSCs, experimental assays are required to determine how to distinguish CSCs from their progeny. Different methods have been used to isolate CSCs from a range of hematopoietic and solid tumors, and some CSC-specific cell surface markers have been found. These markers are primarily selected from the From the ‡Shanghai Key

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A novel human recombinant single-chain antibody targeting CD166/ALCAM inhibits cancer cell invasion in vitro and in vivo tumour growth

Cited by 43 publications

References 33 publications

ALCAM is a Novel Cytoplasmic Membrane Protein in TNF-α Stimulated Invasive Cholangiocarcinoma Cells

ALCAM is a Novel Cytoplasmic Membrane Protein in TNF-α Stimulated Invasive Cholangiocarcinoma Cells

Loss of ALCAM expression is linked to adverse phenotype and poor prognosis in breast cancer: A TMA-based immunohistochemical study on 2,197 breast cancer patients

Plasma Membrane Proteomics of Tumor Spheres Identify CD166 as a Novel Marker for Cancer Stem-like Cells in Head and Neck Squamous Cell Carcinoma

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