B16 Melanoma

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Mus musculus B16F10 skin melanoma cells in laboratory. Mus musculus melanoma skin cancer cells in UFV.jpg
Mus musculus B16F10 skin melanoma cells in laboratory.

B16 melanoma is a murine tumor cell line used for research as a model for human skin cancers. B16 cells are useful models for the study of metastasis and solid tumor formation, and were one of the first effective murine tools for metastasis research. These cells readily metastasize to lymph nodes and lungs. The black melanin pigment they produce facilitates easy visualization of metastatic colonies in these organs. [1]

Contents

History

B16 cells were discovered and maintained in the Jackson Laboratories in Maine in 1954 when a tumor developed naturally behind the ear of a C57BL/6 mouse. [2] The cells were resected, transplanted, and maintained in vivo, and still are today.

B16 models were in use to an extent in the 1970s, but it was Dr. Isaiah J. Fidler, a Jerusalem-born, Oklahoma State-trained veterinarian, and University of Pennsylvania-trained biological researcher, now at M.D. Anderson Cancer Center in Houston, Texas, who established solid protocols for use the B16 model. [3] One of his first major studies involving B16 was in 1970. Dr. Fidler stained B16s, having cultured them in vitro, with 125I-5-iodo-2′-deoxyuridine for tracking, and implanted the cells into C57BL/6J mice, the common host, sacrificed the mice at different times, and measured the cells in the blood and in different organs. [4] He ascertained that 99% of the original cell population had perished within a day, and that a cohort of about 400 cells had colonized the lung. The study was seminal because it established the existence of a reliable metastasis pathway that was uncomplicated to perturb and view changes. It also showed that metastasis is not guaranteed simply by the presence of tumor cells. Only a certain few are able to circulate and latch on to the right organ and begin to form a tumor.

In the 1980s it was discovered that B16 cells express very low levels of mouse class I major histocompatibility complex glycoproteins, H-2Kb and H-2Db, [5] and that in vitro treatment with gamma interferon simultaneously induced a high expression of H-2 and an increase in the metastatic potential of B16 cells. [6]

Characteristics

B16 cells originate in melanin-producing epithelia of mice, and are easy to track in vivo post-transplantation. Their fidelity of metastasis from skin to lung, liver, and spleen makes them useful and predictable tools to study metastatic pathways. [7] [8]

In the 1962 edition of the Handbook of Genetically Standardized Jax Mice, the cells were described thus: [9]

Gross: soft gray tissue, frequently hemorrhagic. Microscopic: tumor cells polyhedral or spindle-shaped, arranged in perivascular mantles and diffuse masses; some cells contain fine pigmented granules, a few are obscured by large, very dark globules of pigment; stoma delicate and vascular. Pigment greatly decreased in comparison with early transplant generation.

Varying surface proteins were shown to play an important part in the locative destiny of the cells on which they are affixed. [10] [11] The presence of high numbers of particular proteins correspond to a cell's affinity for particular organs was selected for in many of the lines perpetuated in labs in the seventies and eighties. Tumor cells from lungs, for instance, would be harvested from a deceased mouse and transplanted into another mouse's skin, and that mouse, upon death, would have its resultant lung tumors transplanted to the next mouse, and so on. Over time, cells in that line injected into the skin would almost always become lung tumors. The same directed etiology, moreover, has been undertaken for many other organs, leading to separate sub-lines with titles such as B16-F10, B16-BL6, B164A5, B16GMCSF, and B16FLT3.

Use in Research

Today, B16 melanoma remains indispensable for metastasis studies. Current research projects focus on the cells’ immunological response to vaccines, microRNA mediated metastatic properties, especially miR-21, a noted aggressor of tumor suppressors and anti-proliferative factors. [12] [13] B16 is also used as a pre-clinical model to study immunotherapy. [14] Those are just a few examples, but the undergirding idea is that the B16 melanoma model is a powerful research tool, and a staple for metastasis studies, and its development as such can be considered a huge benefit to the cancer research community. [2]

Related Research Articles

<span class="mw-page-title-main">Metastasis</span> Spread of a disease inside a body

Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, are metastases (mets). It is generally distinguished from cancer invasion, which is the direct extension and penetration by cancer cells into neighboring tissues.

<span class="mw-page-title-main">Cutaneous squamous-cell carcinoma</span> Medical condition

Cutaneous squamous-cell carcinoma (cSCC), also known as squamous-cell carcinoma of the skin or squamous-cell skin cancer, is one of the three principal types of skin cancer, alongside basal-cell carcinoma and melanoma. cSCC typically presents as a hard lump with a scaly surface, though it may also present as an ulcer. Onset and development often occurs over several months. Compared to basal cell carcinoma, cSCC is more likely to spread to distant areas. When confined to the epidermis, the outermost layer of the skin, the pre-invasive or in situ form of cSCC is termed Bowen's disease.

<span class="mw-page-title-main">Melanoma</span> Cancer originating in melanocytes

Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye. In women, melanomas most commonly occur on the legs; while in men, on the back. Melanoma is frequently referred to as malignant melanoma. However, the medical community stresses that there is no such thing as a 'benign melanoma' and recommends that the term 'malignant melanoma' should be avoided as redundant.

<span class="mw-page-title-main">Cancer stem cell</span> Cancer cells with features of normal cells

Cancer stem cells (CSCs) are cancer cells that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample. CSCs are therefore tumorigenic (tumor-forming), perhaps in contrast to other non-tumorigenic cancer cells. CSCs may generate tumors through the stem cell processes of self-renewal and differentiation into multiple cell types. Such cells are hypothesized to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors. Therefore, development of specific therapies targeted at CSCs holds hope for improvement of survival and quality of life of cancer patients, especially for patients with metastatic disease.

<span class="mw-page-title-main">Uveal melanoma</span> Type of eye cancer

Uveal melanoma is a type of eye cancer in the uvea of the eye. It is traditionally classed as originating in the iris, choroid, and ciliary body, but can also be divided into class I and class II. Symptoms include blurred vision, loss of vision or photopsia, but there may be no symptoms.

Actibind is an actin-binding fungal T(2)-RNase protein that is produced by the black mold Aspergillus niger, a microorganism used in biotechnology and food technology. In plants, actibind binds actin, a major component of the cytoskeleton, interfering with the plants' pollen tubes and halting cell growth. Research published in the journal Cancer on 15 May 2006 reports evidence that actibind has antiangiogenic and anticarcinogenic characteristics. In human colon cancer, breast cancer and melanoma, increasing the level of actibind was found to reduce the ability of these cells to form tumorogenic colonies. In animal models, increased actibind inhibited the growth of colon cancer-derived tumors, metastases and blood vessel formation. During the completion of the Human Genome Project, the gene encoding for RNaseT2, the human actibind-like protein, was found on chromosome 6.

<span class="mw-page-title-main">Ipilimumab</span> Pharmaceutical drug

Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.

<span class="mw-page-title-main">PMEL (gene)</span> Protein-coding gene in the species Homo sapiens

Melanocyte protein PMEL also known as premelanosome protein (PMEL), silver locus protein homolog (SILV) or Glycoprotein 100 (gp100), is a protein that in humans is encoded by the PMEL gene. Its gene product may be referred to as PMEL, silver, ME20, gp100 or Pmel17.

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<span class="mw-page-title-main">TCF21 (gene)</span> Protein-coding gene in the species Homo sapiens

Transcription factor 21 (TCF21), also known as pod-1, capsuling, or epicardin, is a protein that in humans is encoded by the TCF21 gene on chromosome 6. It is ubiquitously expressed in many tissues and cell types and highly significantly expressed in lung and placenta. TCF21 is crucial for the development of a number of cell types during embryogenesis of the heart, lung, kidney, and spleen. TCF21 is also deregulated in several types of cancers, and thus known to function as a tumor suppressor. The TCF21 gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.

<span class="mw-page-title-main">Metastatic breast cancer</span> Type of cancer

Metastatic breast cancer, also referred to as metastases, advanced breast cancer, secondary tumors, secondaries or stage IV breast cancer, is a stage of breast cancer where the breast cancer cells have spread to distant sites beyond the axillary lymph nodes. There is no cure for metastatic breast cancer; there is no stage after IV.

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<span class="mw-page-title-main">Brain metastasis</span> Cancer that has metastasized (spread) to the brain from another location in the body

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Lewis lung carcinoma is a hypermutated Kras/Nras–mutant cancer with extensive regional mutation clusters in its genome. A tumor that spontaneously developed as an epidermoid carcinoma in the lung of a C57BL mouse. It was discovered in 1951 by Dr. Margaret Lewis of the Wistar Institute and became one of the first transplantable tumors.

Skin cancer, or neoplasia, is the most common type of cancer diagnosed in horses, accounting for 45 to 80% of all cancers diagnosed. Sarcoids are the most common type of skin neoplasm and are the most common type of cancer overall in horses. Squamous-cell carcinoma is the second-most prevalent skin cancer, followed by melanoma. Squamous-cell carcinoma and melanoma usually occur in horses greater than 9-years-old, while sarcoids commonly affect horses 3 to 6 years old. Surgical biopsy is the method of choice for diagnosis of most equine skin cancers, but is contraindicated for cases of sarcoids. Prognosis and treatment effectiveness varies based on type of cancer, degree of local tissue destruction, evidence of spread to other organs (metastasis) and location of the tumor. Not all cancers metastasize and some can be cured or mitigated by surgical removal of the cancerous tissue or through use of chemotherapeutic drugs.

<span class="mw-page-title-main">Nivolumab</span> Anticancer medication

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<span class="mw-page-title-main">4T1</span>

4T1 is a breast cancer cell line derived from the mammary gland tissue of a mouse BALB/c strain. 4T1 cells are epithelial and are resistant to 6-thioguanine. In preclinical research, 4T1 cells have been used to study breast cancer metastasis as they can metastasize to the lung, liver, lymph nodes, brain and bone. The cells are known to be highly aggressive in live tissues.

References

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