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306:(DHT), a high-affinity ligand for AR. DHT treatment elicited markedly reduced growth in C4 and C5 cells and no growth in C4-2 cells when compared to the high rate of growth seen in LNCaP cells, suggesting reduced androgen sensitivity in C4 and C5 and AI in C4-2 cells. Whole-cell AR assay also indicated that LNCaP cells have a much higher affinity form of AR (Kd = 159 pM) when compared to C4-2 (Kd = 267 pM).
167:(PCa) research has been the lack of cell lines that closely mimic human disease progression. Two hallmarks of metastatic human prostate cancer include the shift of aggressive PCa from androgen-sensitivity to an Androgen Insensitive (AI) state, and the propensity of PCa to metastasize to bone. Although the generation of AI cell lines has been quite successful as demonstrated in the “classic” cell lines
22:
321:
To generate a bone metastatic subline, C4-2 cells were orthotopically injected into castrated male mice. These cells formed large primary tumors of the prostate, lymph nodes, as well as osseus tumors. Isolation of these osseus tumors resulted in the C4-2B subline. C4-2B cells were positive for PSA
256:
Wu et al. (1994) reproduced the human-derived LNCaP tumors in immunocompromised mice by co-injection of LNCaP cells with MS human bone fibroblasts. Cells were subcutaneously injected at multiple sites into the mouse flank and after approximately 4 weeks of growth, tumors were easily detectable by
312:
C4 and C5 sublines exhibit greatly increased tumorigenicity when injected in intact male mice, unlike parental LNCaP cells. C4 and C5 were also able to form highly vascularized carcinomas in castrated mice when co-injected with MS human fibroblasts. The C4-2 subline more readily forms tumors in
276:
To further verify that these cells were of human origin karyotype analysis determined that the parental LNCaP cells had 7 distinct marker chromosomes, with two copies of each. The M, C4, C5, and C4-2 sublines contained most of the marker chromosomes, with the M subline being most similar to the
260:
To replicate the hallmark shift of PCa cells to AI, LNCaP host mice were castrated by way of midscrotal incision at approximately 8 weeks post injection. Tumors were maintained in castrated hosts for 4 to 5 weeks at which time remaining tumors were harvested. In total, two subsets of cells were
179:
form osteoblastic lesions rather than osteolytic lesions seen in other cancers like breast cancer. Similarly, PC-3 and DU145 cells form osteolytic tumors. To develop an AI-PCa cell model that more closely mimics clinical disease, LNCaP sublines have been generated to provide the most clinically
248:, Male mice develop tumors earlier and at a greater frequency than do females and hormonal manipulations show that the frequency of tumor development correlates with serum androgen levels. The rate of the tumor growth, however, is independent of the gender or hormonal status of the host.
313:
intact hosts than C4 and C5 sublines and they are the only cells able to form tumors in castrated host without co-injection of MS human bone fibroblasts. These same C4-2 tumors stained for PSA and secreted high levels of PSA into the growth medium.
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cells were derived from LNCaP cultured in RPMI-1640 (without phenol red) with 10% charcoal stripped fetal bovine serum. LN95 cells differ from parental LNCaP cells morphologically, with pronounced dendritic extensions, and molecularly, with
326:, confirming their prostatic origin. Most importantly, immunohistochemical staining of the C4-2B tumors were positive for osteoblast activity suggesting the induction of osteoblastic tumor formation mirroring the progression of human PCa.
407:, low expression of AR-V7, and remain androgen responsive. The mechanism of the highly proliferative phenotype of LNCaP-AI cells appears to be loss of cell cycle regulator expression (p21, p16) and increased anti-apoptotic
474:
Thalmann GN, Anezinis PE, Chang SM, Zhau HE, Kim EE, Hopwood VL, Pathak S, von
Eschenbach AC, Chung LW (May 1994). "Androgen-independent cancer progression and bone metastasis in the LNCaP model of human prostate cancer".
208:
was established from a metastatic lesion of human prostatic adenocarcinoma. The LNCaP cells grow readily in vitro (up to 8 x 10 cells/sq cm; doubling time, 60 hr), form clones and are highly resistant to human fibroblast
284:
C4, C5, and C4-2 sublines grow well under identical tissue culture conditions as LNCaP with similar growth rates. Parental LNCaP, M, C4, and C5 subline have similar baseline gene expression levels of
264:
To further select for AI-PCa cells, the C4 subline was co-injected with MS human fibroblasts into a castrated host. The resulting tumors were isolated and an additional subline was generated, C4-2.
277:
parental LNCaP cells. C4, C5 and C4-2 are only minutely distinct from LNCaP and the M subline with the addition of a marker chromosome resulting from a segment addition to chromosome 6. A
403:(or LN-AI) cells were derived from 6-Month culture of LNCaP parental cells in charcoal stripped serum. While LNCaP-AI are wholly androgen independent, they retain high expression of
645:
Wu HC, Hsieh JT, Gleave ME, Brown NM, Pathak S, Chung LW (May 1994). "Derivation of androgen-independent human LNCaP prostatic cancer cell sublines: role of bone stromal cells".
273:
indicate that LNCaP cells grown in intact hosts (M subline) have a modal chromosomal distribution number of 83, C4 and C5 sublines with 85, and the C4-2 subline with 83.
691:
Pflug, BR; Reiter, RE; Nelson, JB (1 September 1999). "Caveolin expression is decreased following androgen deprivation in human prostate cancer cell lines".
526:"Osteomimetic properties of prostate cancer cells: a hypothesis supporting the predilection of prostate cancer metastasis and growth in the bone environment"
337:
formation), C4-2B cells produce and retain approximately 8x more mineralized calcium than parental LNCaP cells. C4-2B cells also express higher levels of
217:. The malignant properties of LNCaP cells are maintained in athymic nude mice which develop tumors at the injection site and show a similar doubling time
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Horoszewicz JS, Leong SS, Kawinski E, Karr JP, Rosenthal H, Chu TM, Mirand EA, Murphy GP (April 1983). "LNCaP model of human prostatic carcinoma".
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880:"Determination of tag density required for digital transcriptome analysis: application to an androgen-sensitive prostate cancer model"
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373:, a known inducer of Cbfa1, is also more highly expressed in C4-2B cells, further suggesting many osteoblast-like properties.
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43:
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from a 50-year-old caucasian male in 1977. They are adherent epithelial cells growing in aggregates and as single cells.
175:, the behavior of these cells in bone does not fully mimic clinical human disease. It is well established that human PCa
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292:(PSA) however, M, C4, and C5 sublines express 5-10X more PSA mRNA. M, C4, C5 and C4-2 also expressed reduced human
213:. LNCaP cells have a modal chromosome number of 76 to 91, indicative of a human male karyotype with several marker
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5 alpha-dihydrotestosterone modulation of cell growth and acid phosphatase production. LNCaP cells also express
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cells. Notably, LN95 cells are significantly more tumour initiating than their parental counterparts
365:. Osteoblast promoter activity is also higher in C4-2B cells when compared to LNCaP, as indicated by
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795:"Molecular mechanisms of androgen-independent growth of human prostate cancer LNCaP-AI cells"
333:(known to promote skeletal-like ECM formation in osteoblasts) and a source of phosphate (for
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Lin DL, Tarnowski CP, Zhang J, Dai J, Rohn E, Patel AH, Morris MD, Keller ET (May 2001).
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is not present in most C4, C5 and C4-2 cells, suggesting major chromosomal alterations.
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570:"Bone metastatic LNCaP-derivative C4-2B prostate cancer cell line mineralizes in vitro"
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Representative phase-contrast image of LNCaP cells. Scale bars represent 100 ÎĽm.
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collected from castrated hosts: C4 and C5, collected at 4 and 5 weeks respectively.
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836:"In vitro model systems to study androgen receptor signaling in prostate cancer"
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receptors are present in the cytosol and nuclear fractions. The LNCaP line is
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Liu, LL; Xie, N; Sun, S; Plymate, S; Mostaghel, E; Dong, X (12 June 2014).
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10.1002/(sici)1097-0045(19990901)40:4<269::aid-pros9>3.0.co;2-6
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10.1002/(SICI)1097-0045(19990601)39:4<246::AID-PROS5>3.0.CO;2-U
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739:"Mechanisms of the androgen receptor splicing in prostate cancer cells"
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Sampson, N; Neuwirt, H; Puhr, M; Klocker, H; Eder, IE (April 2013).
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physical examination and had a high rate of growth (17-33 mm3/day).
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One major obstacle to conducting the most clinically relevant
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Li H, Lovci MT, Kwon YS, Rosenfeld MG, Fu XD, Yeo GW (2008).
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When cultured in a “promineralization medium” that contains
504:"LNCaP Cell Line: human prostate adenocarcinoma cell line"
503:
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cells derived from the left supraclavicular lymph node
46:. Unsourced material may be challenged and removed.
361:(OSN) mRNA, all of which are highly expressed by
369:transcription factor expression. Concomitantly,
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141:of human cells commonly used in the field of
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524:Koeneman KS, Yeung F, Chung LW (June 1999).
389:variant expression similar to that of AR-V7
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106:Learn how and when to remove this message
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180:relevant tissue culture tools to date.
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44:adding citations to reliable sources
130:Properties of common PCa cell lines
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941:Transfection data on LNCaP Cells
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302:All sublines were treated with
31:needs additional citations for
296:mRNA as expected in AI cells.
1:
377:Androgen Independent Variants
961:Cellosaurus entry for C4-2B
946:Cellosaurus entry for LNCaP
1007:
956:Cellosaurus entry for C4-2
290:Prostate Specific Antigen
242:Prostate Specific Antigen
966:Cellosaurus entry for C5
951:Cellosaurus entry for C4
840:Endocrine-Related Cancer
812:10.1210/endo.140.11.7086
905:10.1073/pnas.0807121105
286:ornithine decarboxylase
224:High-affinity specific
884:Proc Natl Acad Sci USA
659:10.1002/ijc.2910570319
502:Fanelli, Alex (2016).
300:Androgen Insensitivity
131:
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236:responsive, shown by
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755:10.1038/onc.2013.284
343:alkaline phosphatase
40:improve this article
896:2008PNAS..10520179L
853:10.1530/ERC-12-0401
304:dihydrotestosterone
145:. LNCaP cells are
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793:(November 1999).
789:Lu, S; Tsai, SY;
589:10.1002/pros.1065
405:Androgen receptor
387:Androgen receptor
347:bone sialoprotein
294:androgen receptor
149:-sensitive human
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38:Please help
33:verification
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363:osteoblasts
359:Osteonectin
351:Osteocalcin
271:comparisons
215:chromosomes
188:The LNCaP (
975:Categories
509:3 December
477:Cancer Res
446:Cancer Res
415:References
288:(ODC) and
234:hormonally
211:interferon
158:metastasis
66:newspapers
269:Karyotype
206:cell line
204:rostate)
139:cell line
924:19088194
862:23447570
821:10537131
791:Tsai, MJ
773:23851510
743:Oncogene
721:19432542
713:10420156
675:22056818
615:31076493
607:11351351
577:Prostate
552:10344214
530:Prostate
401:LNCaP-AI
238:in vitro
230:estrogen
226:androgen
151:prostate
147:androgen
143:oncology
915:2603435
892:Bibcode
764:4553036
667:8169003
489:8168083
458:6831420
395:in vivo
353:(OCN),
349:(BSP),
341:(OPG),
246:In vivo
244:(PSA).
219:in vivo
184:History
80:scholar
55:"LNCaP"
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717:S2CID
671:S2CID
611:S2CID
573:(PDF)
367:Cbfa1
355:RANKL
317:C4-2B
192:ymph
169:DU145
135:LNCaP
87:JSTOR
73:books
920:PMID
858:PMID
817:PMID
769:PMID
709:PMID
663:PMID
603:PMID
548:PMID
511:2017
485:PMID
454:PMID
409:Bcl2
391:VCaP
382:LN95
371:BMP7
322:and
228:and
196:ode
171:and
59:news
910:PMC
900:doi
888:105
848:doi
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759:PMC
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