Pancreatic tumor cell lines

Tan, M. H. and Chu, T. M. (1985). Characterization of the tumorigenic and metastatic properties of a human pancreatic tumor cell line (ASPC-1). implanted orthotopically into nude mice. Tumor Biol. 6, 89-98. 

Variations in the expression of angiogenic factors may modulate tumor vascularization and therefore oxygenation. This, in turn, may contribute to differing responsiveness to treatments between different tumor cell types. For example, increased radioresistance in pancreatic carcinoma cell lines was associated with an increased expression of angiopoietin (Ang)-2, which plays an important role in vascular maturation [56]. 

Yanagihara, K.,Oka, M., Yamaguchi, K. (2002). Peptidomics-based approach reveals the secretion of the 29-residue COO H-terminal fragment of the putative tumor suppressor protein DMBTl from pancreatic adenocarcinoma cell lines. Cancer Res. 62, 4894-4898. 

The biological functions of the lipo-gastrin and lipo-CCK peptides were analyzed on these two receptors of known sequence using rat pancreatic acinar cells and the tumoral rat pancreatic acinar cell line AR42J. The CCK-A receptor has been thoroughly characterized in the rat pancreatic acinar cells (140-142) and in its... 

In contrast to ILK, overexpression of the prosurvival integrin signaling mediator FAK protects leukemia cells from radiation- and chemo-induced apoptosis (Kasa-HARA et al. 2002). Silencing of FAK protein expression with siRNA mediated knockdown increases the radiosensitivity of different tumor cell lines originating from pancreatic cancer (Cordes et al. 2007), breast cancer, and colorectal cancer (McLean etaL 2005). Others have shown that human melanoma cells become more sensitive to the chemotherapeutic agent 5-fluorouracil when FAK expression is downregulated (Smith etal. 2005). 

A number of studies reported in the literature reveal wide array of polyphenol compounds derived from common dietary sources and medicinal plants wield antitumor effects through the suppression of NF-kB DNA binding activity in myeloid, lymphoid, and several solid tumor cell lines derived from prostate, breast, head and neck, and pancreatic cancer cells resulting in the inhibition of downstream target genes that are critical for the establishment of aggressive cancers. This ultimately leads to the inhibition of cell growth and induction of apoptotic cell death [118-120]. 

Additionally, several reports indicate that -resveratrol inhibits the proliferation of a wide variety of human cancer cells including breast, prostate, colon, gastric, lung, pancreatic, liver, thyroid, and ovarian cancers, leukemia, lymphoma, osteosarcoma, squamous cell carcinoma, multiple myeloma, and medulloblastoma [135]. Among the other stilbenoids, piceatannol, a- and s-viniferin, hopeaphenol, pallidol, ampelopsin A, vaticanol B and C, and pterostilbene also showed cytotoxicity and/or antiproliferative effect on different tumor cell lines [136-145]. 

After using C A19-9 as the only accepted diagnostic marker for pancreatic cancer for two decades [92], a bewildering number of potential biomarkers are currently under evaluation [93]. Apeak (3334.7 Da) found by SELDI-TOF-MS in 5/15 pancreatic adenocarcinoma cell lines was identified by Qq-TOF-MS/MS as the COOH-terminal fragment of DMBTl, a putative tumor suppression protein intracellularly generated by Umited prior proteolysis. Analyses of other cell lines suggested that the marker may be unique to pancreatic adenocarcinoma [94]. In another study, a differentially expressed peak (—16,570 Da) was detected in 10/15 samples from pancreatic adenocarcinoma in contrast to only 1/7 with other pancreatic diseases. The peak was identified as hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein I (HIP-PAP I) by SELDI immunoassay [95]. 

In mouse tissuse, p3GalT-I and -II are expressed at high levels in the brain whereas p3GalT-III was expressed at comparable levels in brain, ovary, uterus and stomach [35]. In contrast P3GalT-V is expressed primarily in gastrointestinal and pancreatic epithelia and in established tumor cell lines derived from these tissues... 

Campbell and Der 2004). AKT, in turn, has been shown to activate eNOS through phosphorylation of SI 177 in endothelial cells. We thus tested whether eNOS is phosphorylated and thereby activated at the AKT site SI 177 in the cancer most characterized by oncogenic Ras mutations, human pancreatic cancer (Bos 1989). A panel of nine pancreatic cancer cell lines and two normal pancreatic tissue specimens were immunoblotted with an a-phospho(S 1177)-eNOS antibody (Chen et al. 1999 Michell et al. 1999), with the finding that S1177 phosphorylation of eNOS was elevated in a subset of the mmor cell lines samples compared to the normal tissue control (Fig. 2.2a and (Lim et al. 2008)). We extended these results to acmal pancreatic cancer tumor specimens, only this time finding an increase in SI 177 phosphorylation in all tumor samples compared to the matched and unmatched normal controls (Fig. 2.2b and (Lim et al. 2008)). eNOS is thus phosphorylated at the AKT site SI 177 in Ras-driven human pancreatic cancer specimens. 

Fig. 2.2 eNOS is phosphorylated at SI 177 in oncogenic KRas-driven tumors. Immunoblot of (a) indicated human pancreatic cancer cell lines or (b) pancreatic biopsies of non-malignant (N) and tumor (T) tissue with an a-phospho(Sl 177)-eNOS antibody. Actin and tubulin loading controls. Adapted from (Lim et al. 2008) and used with permission from the publisher... 

When the chemosensitive human pancreatic carcinoma cell lines T3M4 and PT45-P1 were kept in coculture with fibroblasts, both cell lines became much less sensitive toward treatment with etoposide. The chemoresistant future of T3M4 and PT45-P1 cells was increased by the NO production from neighboring fibroblasts which exhibited significant iNOS expression and NO secretion. This suggests that there were tumor-stromal fibroblast interactions in the chemoresistance of pancreatic carcinoma due to NO production (Muerkoster et al. 2004). 

In precHnical models, ARRY-142886 treatment results in either tumor regression or stasis in xenograft models of colorectal, non-small cell lung, pancreatic, breast, and melanoma cancers. Most of these cell lines contain either the B-Raf or K-Ras mutations. Complete inhibition of pERKl/2 formation in excised tumors from both HT-29 and BxPC3 studies was achieved 4 h after an oral dose of 20 mg/kg/day ARRY-142886 [114]. In a separate HT-29 study, a PK/PD relationship was established [115]. Twelve hours after a single 30 mg/kg oral dose of ARRY-142886, approximately 80% inhibition of ERKl/2 phosphorylation was observed with a corresponding plasma concentration of about 0.60 xg/ml. In the same study at 24 h, ERKl/2 phosphorylation was... 

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